PanelApp (test)

Activity

Filter

Cancel
Date Panel Item Activity
3000 actions
Mendeliome v0.9028 ABCG5 Zornitza Stark reviewed gene: ABCG5: Rating: GREEN; Mode of pathogenicity: None; Publications: 34304999, 33907061, 32546081, 23556150; Phenotypes: Sitosterolaemia 2, MIM# 618666; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9028 CLCN3 Zornitza Stark Phenotypes for gene: CLCN3 were changed from Neurodevelopmental disorder with hypotonia and brain abnormalities, MIM# 619512 to Neurodevelopmental disorder with hypotonia and brain abnormalities, MIM# 619512; Neurodevelopmental disorder with seizures and brain abnormalities, MIM# 619517
Mendeliome v0.9027 CLCN3 Zornitza Stark edited their review of gene: CLCN3: Changed phenotypes: Neurodevelopmental disorder with hypotonia and brain abnormalities, MIM# 619512, Neurodevelopmental disorder with seizures and brain abnormalities, MIM# 619517
Mendeliome v0.9027 CLCN3 Zornitza Stark Phenotypes for gene: CLCN3 were changed from Neurodevelopmental disorder to Neurodevelopmental disorder with hypotonia and brain abnormalities, MIM# 619512
Mendeliome v0.9026 CLCN3 Zornitza Stark reviewed gene: CLCN3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and brain abnormalities, MIM# 619512; Mode of inheritance: None
Mendeliome v0.9026 TOM1 Zornitza Stark Marked gene: TOM1 as ready
Mendeliome v0.9026 TOM1 Zornitza Stark Gene: tom1 has been classified as Red List (Low Evidence).
Mendeliome v0.9026 TOM1 Zornitza Stark gene: TOM1 was added
gene: TOM1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TOM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TOM1 were set to 31263572
Phenotypes for gene: TOM1 were set to Immunodeficiency 85 and autoimmunity, MIM# 619510
Review for gene: TOM1 was set to RED
Added comment: Parent and child reported with onset of atopic eczema and recurrent respiratory infections in the first decade of life; autoimmune enteropathy with vomiting, diarrhoea, and poor overall growth. More variable features included autoimmune oligoarthritis, interstitial pneumonitis, and EBV viremia. Laboratory studies showed hypogammaglobulinaemia and abnormal T-cell function, consistent with a combined immunodeficiency. Missense variant in TOM1, with limited functional data.
Sources: Expert list
Mendeliome v0.9025 ARF1 Arina Puzriakova reviewed gene: ARF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28868155, 34353862; Phenotypes: Periventricular nodular heterotopia 8, OMIM:618185; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9025 GINS2 Arina Puzriakova gene: GINS2 was added
gene: GINS2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GINS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GINS2 were set to 34353863
Phenotypes for gene: GINS2 were set to Meier-Gorlin syndrome with craniosynostosis
Review for gene: GINS2 was set to RED
Added comment: Sa et al., 2021 (PMID: 34353863) identified a patient presenting with prenatal and postnatal growth restriction, a craniofacial gestalt of MGORS and coronal craniosynostosis. A homozygous missense variant (c.341G>T, p.Arg114Leu) in GINS2 was identified that was heterozygous in both unaffected parents. Some supportive functional data included.

GINS2 is not currently not associated with any phenotype in OMIM or G2P and no additional cases have been identified to date.
Sources: Literature
Mendeliome v0.9025 DNAH10 Zornitza Stark Phenotypes for gene: DNAH10 were changed from primary male infertility with asthenoteratozoospermia to Spermatogenic failure 56, MIM# 619515
Mendeliome v0.9024 DNAH10 Zornitza Stark reviewed gene: DNAH10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 56, MIM# 619515; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9024 GNB2 Zornitza Stark Phenotypes for gene: GNB2 were changed from intellectual disability; dysmorphic features to Neurodevelopmental disorder with hypotonia and dysmorphic facies 619503
Mendeliome v0.9023 GNB2 Zornitza Stark edited their review of gene: GNB2: Changed phenotypes: Neurodevelopmental disorder with hypotonia and dysmorphic facies, MIM# 619503
Mendeliome v0.9023 KIDINS220 Zornitza Stark Phenotypes for gene: KIDINS220 were changed from Spastic paraplegia, intellectual disability, nystagmus, and obesity, MIM# 617296; cerebral ventriculomegaly; limb contractures to Spastic paraplegia, intellectual disability, nystagmus, and obesity, MIM# 617296; Ventriculomegaly and arthrogryposis, MIM# 619501
Mendeliome v0.9022 KIDINS220 Zornitza Stark edited their review of gene: KIDINS220: Changed phenotypes: Spastic paraplegia, intellectual disability, nystagmus, and obesity, MIM# 617296, Ventriculomegaly and arthrogryposis, MIM# 619501
Mendeliome v0.9022 CHRM1 Bryony Thompson Marked gene: CHRM1 as ready
Mendeliome v0.9022 CHRM1 Bryony Thompson Gene: chrm1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9022 CHRM1 Bryony Thompson Classified gene: CHRM1 as Amber List (moderate evidence)
Mendeliome v0.9022 CHRM1 Bryony Thompson Gene: chrm1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9021 CHRM1 Bryony Thompson gene: CHRM1 was added
gene: CHRM1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CHRM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHRM1 were set to 34212451; 31981491; 12483218
Phenotypes for gene: CHRM1 were set to Neurodevelopmental delay; intellectual disability; autism
Review for gene: CHRM1 was set to AMBER
Added comment: PMID: 34212451 - 2 unrelated cases with de novo missense variants (p.Pro380Leu and p.Phe425Ser), one case with early-onset refractory epilepsy, severe disability, and progressive cerebral and cerebellar atrophy, and the second case with mild dysmorphism, global developmental delay, and moderate intellectual disability. In vitro biochemical analyses of p.Pro380Leu demonstrated a reduction in protein levels, impaired cellular trafficking, and defective activation of intracellular signaling pathways.
PMID: 31981491 - an autism spectrum disorder (no other information on phenotype, except ascertained to have severe neurodevelopmental delay) case with a de novo missense variant p.(Arg210Leu)
PMID: 12483218 - null mouse model assessing memory demonstrated selective cognitive dysfunction.
Sources: Literature
Mendeliome v0.9020 FGF20 Zornitza Stark Marked gene: FGF20 as ready
Mendeliome v0.9020 FGF20 Zornitza Stark Gene: fgf20 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9020 FGF20 Zornitza Stark Classified gene: FGF20 as Amber List (moderate evidence)
Mendeliome v0.9020 FGF20 Zornitza Stark Gene: fgf20 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9019 FGF20 Zornitza Stark gene: FGF20 was added
gene: FGF20 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: FGF20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FGF20 were set to 22698282
Phenotypes for gene: FGF20 were set to Renal hypodysplasia/aplasia 2, MIM#615721
Review for gene: FGF20 was set to AMBER
Added comment: Multiple affected fetuses in a consanguineous family; functional data.
Sources: Expert Review
Mendeliome v0.9018 ITGA8 Zornitza Stark Marked gene: ITGA8 as ready
Mendeliome v0.9018 ITGA8 Zornitza Stark Gene: itga8 has been classified as Green List (High Evidence).
Mendeliome v0.9018 ITGA8 Zornitza Stark Phenotypes for gene: ITGA8 were changed from to Renal hypodysplasia/aplasia 1, MIM# 191830
Mendeliome v0.9017 ITGA8 Zornitza Stark Publications for gene: ITGA8 were set to
Mendeliome v0.9016 ITGA8 Zornitza Stark Mode of inheritance for gene: ITGA8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9015 ITGA8 Zornitza Stark reviewed gene: ITGA8: Rating: GREEN; Mode of pathogenicity: None; Publications: 24439109; Phenotypes: Renal hypodysplasia/aplasia 1, MIM# 191830; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9015 NPR2 Zornitza Stark Marked gene: NPR2 as ready
Mendeliome v0.9015 NPR2 Zornitza Stark Gene: npr2 has been classified as Green List (High Evidence).
Mendeliome v0.9015 NPR2 Zornitza Stark Phenotypes for gene: NPR2 were changed from to Acromesomelic dysplasia, Maroteaux type MIM# 602875; Epiphyseal chondrodysplasia, Miura type, MIM# 615923; Short stature with nonspecific skeletal abnormalities, MIM# 616255
Mendeliome v0.9014 NPR2 Zornitza Stark Publications for gene: NPR2 were set to
Mendeliome v0.9013 NPR2 Zornitza Stark Mode of inheritance for gene: NPR2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9012 NPR2 Zornitza Stark changed review comment from: Over 15 unrelated families; Biallelic (missense, nonsense, frameshift, splice) NPR2 variants; loss of function; multiple mouse models.

Disorder is characterised by severe dwarfism with shortening of the middle and distal segments of the limbs (disproportionate) with skeletal growth falling off sharply after birth.; to: Bi-allelic variants: Over 15 unrelated families; Biallelic (missense, nonsense, frameshift, splice) NPR2 variants; loss of function; multiple mouse models.

Disorder is characterised by severe dwarfism with shortening of the middle and distal segments of the limbs (disproportionate) with skeletal growth falling off sharply after birth.

Mono-allelic variants have been linked to both tall stature and short stature disorders. Multiple families.
Mendeliome v0.9012 NPR2 Zornitza Stark edited their review of gene: NPR2: Changed publications: 31555216, 16384845, 15146390, 22870295, 24057292, 24259409, 16384845, 24471569; Changed phenotypes: Acromesomelic dysplasia, Maroteaux type MIM# 602875, Epiphyseal chondrodysplasia, Miura type, MIM# 615923, Short stature with nonspecific skeletal abnormalities, MIM# 616255; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9012 NPR2 Zornitza Stark reviewed gene: NPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31555216, 16384845, 15146390; Phenotypes: Acromesomelic dysplasia, Maroteaux type MIM# 602875, Short stature, disproportionate, Oval vertebral bodies in infancy, Progressive shortening of humerus, radius and ulna in first year, dwarfism, Prominent forehead; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9012 RPS6KA3 Zornitza Stark Marked gene: RPS6KA3 as ready
Mendeliome v0.9012 RPS6KA3 Zornitza Stark Gene: rps6ka3 has been classified as Green List (High Evidence).
Mendeliome v0.9012 RPS6KA3 Zornitza Stark Phenotypes for gene: RPS6KA3 were changed from to Coffin-Lowry syndrome MIM# 303600; Intellectual disability; short stature; delayed bone age; hearing deficit; hypotonia; tapering fingers; abnormal facies (hypertelorism, anteverted nares, prominent frontal region)
Mendeliome v0.9011 RPS6KA3 Zornitza Stark Publications for gene: RPS6KA3 were set to
Mendeliome v0.9010 RPS6KA3 Zornitza Stark Mode of inheritance for gene: RPS6KA3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.9009 RPS6KA3 Zornitza Stark reviewed gene: RPS6KA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 6879200; Phenotypes: Coffin-Lowry syndrome MIM# 303600, Intellectual disability, short stature, delayed bone age, hearing deficit, hypotonia, tapering fingers, abnormal facies (hypertelorism, anteverted nares, prominent frontal region); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.9009 SHOX2 Zornitza Stark Marked gene: SHOX2 as ready
Mendeliome v0.9009 SHOX2 Zornitza Stark Gene: shox2 has been classified as Red List (Low Evidence).
Mendeliome v0.9009 SHOX2 Zornitza Stark gene: SHOX2 was added
gene: SHOX2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: SHOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SHOX2 were set to 30443179
Phenotypes for gene: SHOX2 were set to Sinus Node Dysfunction; Atrial Fibrillation
Review for gene: SHOX2 was set to RED
Added comment: Single family reported with LoF in this gene and AF.
Sources: Expert Review
Mendeliome v0.9007 KCTD7 Zornitza Stark Marked gene: KCTD7 as ready
Mendeliome v0.9007 KCTD7 Zornitza Stark Gene: kctd7 has been classified as Green List (High Evidence).
Mendeliome v0.9007 KCTD7 Zornitza Stark Phenotypes for gene: KCTD7 were changed from to Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (MIM#611726)
Mendeliome v0.9006 KCTD7 Zornitza Stark Publications for gene: KCTD7 were set to
Mendeliome v0.9005 KCTD7 Zornitza Stark Mode of inheritance for gene: KCTD7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9004 KCTD7 Kristin Rigbye reviewed gene: KCTD7: Rating: GREEN; Mode of pathogenicity: None; Publications: 22693283, 22748208; Phenotypes: Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (MIM#611726), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9004 ANKRD17 Zornitza Stark Phenotypes for gene: ANKRD17 were changed from Intellectual disability; dysmorphic features to Chopra-Amiel-Gordan syndrome, MIM# 619504; Intellectual disability; dysmorphic features
Mendeliome v0.9003 ANKRD17 Zornitza Stark edited their review of gene: ANKRD17: Changed phenotypes: Chopra-Amiel-Gordan syndrome, MIM# 619504, Intellectual disability, dysmorphic features
Mendeliome v0.9003 ROR2 Zornitza Stark Marked gene: ROR2 as ready
Mendeliome v0.9003 ROR2 Zornitza Stark Gene: ror2 has been classified as Green List (High Evidence).
Mendeliome v0.9003 ROR2 Zornitza Stark Phenotypes for gene: ROR2 were changed from to Robinow syndrome, autosomal recessive MIM# 268310; hypertelorism; short stature; mesomelic shortening of the limbs; hypoplastic genitalia; rib/vertebral anomalies; abnormal morphogenesis of the face; Brachydactyly, type B1 MIM# 113000; hypoplasia/aplasia of distal phalanges and nails (2-5)
Mendeliome v0.9002 ROR2 Zornitza Stark Publications for gene: ROR2 were set to
Mendeliome v0.9001 ROR2 Zornitza Stark Mode of inheritance for gene: ROR2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9000 ROR2 Zornitza Stark reviewed gene: ROR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10932186, 10932187, 10986040, 19461659; Phenotypes: Robinow syndrome, autosomal recessive MIM# 268310, hypertelorism, short stature, mesomelic shortening of the limbs, hypoplastic genitalia, rib/vertebral anomalies, abnormal morphogenesis of the face, Brachydactyly, type B1 MIM# 113000, hypoplasia/aplasia of distal phalanges and nails (2-5); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9000 PROP1 Zornitza Stark Marked gene: PROP1 as ready
Mendeliome v0.9000 PROP1 Zornitza Stark Gene: prop1 has been classified as Green List (High Evidence).
Mendeliome v0.9000 PROP1 Zornitza Stark Phenotypes for gene: PROP1 were changed from to Pituitary hormone deficiency, combined, 2 MIM# 262600; Ateliotic dwarfism with hypogonadism; growth failure; short stature; failure to thrive; absent sexual development at puberty; GH, PRL, TSH, LH, and FSH deficiency; pituitary hypoplasia
Mendeliome v0.8999 PROP1 Zornitza Stark Publications for gene: PROP1 were set to
Mendeliome v0.8998 PROP1 Zornitza Stark Mode of inheritance for gene: PROP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8997 PROP1 Zornitza Stark reviewed gene: PROP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301521, 31090814; Phenotypes: Pituitary hormone deficiency, combined, 2 MIM# 262600, Ateliotic dwarfism with hypogonadism, growth failure, short stature, failure to thrive, absent sexual development at puberty, GH, PRL, TSH, LH, and FSH deficiency, pituitary hypoplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8997 WRN Zornitza Stark Marked gene: WRN as ready
Mendeliome v0.8997 WRN Zornitza Stark Gene: wrn has been classified as Green List (High Evidence).
Mendeliome v0.8997 WRN Zornitza Stark Phenotypes for gene: WRN were changed from to Werner syndrome, MIM# 277700; MONDO:0010196
Mendeliome v0.8996 WRN Zornitza Stark Publications for gene: WRN were set to
Mendeliome v0.8995 WRN Zornitza Stark Mode of inheritance for gene: WRN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8994 WRN Zornitza Stark reviewed gene: WRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 28476236, 8602509, 8968742, 9012406; Phenotypes: Werner syndrome, MIM# 277700, MONDO:0010196; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8994 POU1F1 Zornitza Stark Marked gene: POU1F1 as ready
Mendeliome v0.8994 POU1F1 Zornitza Stark Gene: pou1f1 has been classified as Green List (High Evidence).
Mendeliome v0.8994 POU1F1 Zornitza Stark Phenotypes for gene: POU1F1 were changed from to Pituitary hormone deficiency, combined, 1 MIM# 613038; pituitary hypoplasia; severe growth failure; combined GH, PRL and TSH deficiency; distinct facial features (prominent forehead, mid-facial hypoplasia, depressed nasal bridge, deep-set eyes and a short nose with anteverted nostrils)
Mendeliome v0.8993 POU1F1 Zornitza Stark Publications for gene: POU1F1 were set to
Mendeliome v0.8992 POU1F1 Zornitza Stark Mode of inheritance for gene: POU1F1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8991 POU1F1 Zornitza Stark reviewed gene: POU1F1: Rating: GREEN; Mode of pathogenicity: None; Publications: 1302000, 1472057, 9392392, 15928241, 7833912, 12773133; Phenotypes: Pituitary hormone deficiency, combined, 1 MIM# 613038, pituitary hypoplasia, severe growth failure, combined GH, PRL and TSH deficiency, distinct facial features (prominent forehead, mid-facial hypoplasia, depressed nasal bridge, deep-set eyes and a short nose with anteverted nostrils); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8991 OPDM2 Bryony Thompson Marked STR: OPDM2 as ready
Mendeliome v0.8991 OPDM2 Bryony Thompson Str: opdm2 has been classified as Green List (High Evidence).
Mendeliome v0.8991 OPDM2 Bryony Thompson Classified STR: OPDM2 as Green List (high evidence)
Mendeliome v0.8991 OPDM2 Bryony Thompson Str: opdm2 has been classified as Green List (High Evidence).
Mendeliome v0.8990 OPDM2 Bryony Thompson STR: OPDM2 was added
STR: OPDM2 was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: OPDM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: OPDM2 were set to 32413282; 33374016
Phenotypes for STR: OPDM2 were set to Oculopharyngodistal myopathy 2 MIM#618940
Review for STR: OPDM2 was set to GREEN
STR: OPDM2 was marked as clinically relevant
Added comment: NM_005716.4:c.-211GGC[X]
>15 Chinese families/probands with a heterozygous trinucleotide repeat expansion (CGG(n)) in 5'UTR exon 1 of the GIPC1 gene. The expansion was found by a combination of linkage analysis, whole-exome sequencing, long-range sequencing, and PCR analysis, and segregated with the disorder in the family. Repeat lengths in the patients ranged from 70 to 138. Normal repeat lengths ranged from 12 to 32.
Sources: Literature
Mendeliome v0.8989 FAME2 Bryony Thompson Marked STR: FAME2 as ready
Mendeliome v0.8989 FAME2 Bryony Thompson Str: fame2 has been classified as Green List (High Evidence).
Mendeliome v0.8989 GIPC1 Bryony Thompson Classified gene: GIPC1 as No list
Mendeliome v0.8989 GIPC1 Bryony Thompson Added comment: Comment on list classification: Added to panel as an STR under OPDM2
Mendeliome v0.8989 GIPC1 Bryony Thompson Gene: gipc1 has been removed from the panel.
Mendeliome v0.8988 FAME2 Bryony Thompson Classified STR: FAME2 as Green List (high evidence)
Mendeliome v0.8988 FAME2 Bryony Thompson Str: fame2 has been classified as Green List (High Evidence).
Mendeliome v0.8987 FAME2 Bryony Thompson STR: FAME2 was added
STR: FAME2 was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: FAME2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: FAME2 were set to 11701600; 24114805; 31664034
Phenotypes for STR: FAME2 were set to Epilepsy, familial adult myoclonic, 2 MIM#607876
Review for STR: FAME2 was set to GREEN
STR: FAME2 was marked as clinically relevant
Added comment: NM_020151.3(STARD7):c.291-1572ATTTT[X]ATTTC[X]
158 affected individuals from 22 unrelated families with familial adult myoclonic epilepsy with a heterozygous 5-bp repeat expansion (ATTTC)n in intron 1. Affected individuals had variable expansion of an endogenous (ATTTT)n repeat in addition to the insertion of an abnormal (ATTTC)n repeat, similar molecular finding in other forms of FAME. RNA sequencing from patient derived fibroblasts shows no accumulation of the AUUUU or AUUUC repeat sequences and no effect on STARD7 gene expression, suggesting ATTTC expansions may cause FAME irrespective of the genomic locus involved.
Sources: Literature
Mendeliome v0.8986 STARD7 Bryony Thompson Classified gene: STARD7 as No list
Mendeliome v0.8986 STARD7 Bryony Thompson Added comment: Comment on list classification: Added to panel as an STR under FAME2
Mendeliome v0.8986 STARD7 Bryony Thompson Gene: stard7 has been removed from the panel.
Mendeliome v0.8985 PNPLA6 Zornitza Stark Publications for gene: PNPLA6 were set to 25480986; 24355708
Mendeliome v0.8984 PNPLA6 Zornitza Stark changed review comment from: Ataxia is part of the phenotype.
Sources: Expert list; to: Variants in this gene are associated with multiple phenotypes.

Oliver-McFarlane syndrome is a rare congenital disorder characterized by trichomegaly, severe chorioretinal atrophy and multiple pituitary hormone deficiencies, including growth hormone. At least 10 families reported.

Laurence-Moon syndrome has a clinical presentation similar to that of Oliver-McFarlane syndrome, including chorioretinopathy and pituitary dysfunction, but with childhood onset of ataxia, peripheral neuropathy, and spastic paraplegia and without trichomegaly. Single family reported.
Mendeliome v0.8984 PNPLA6 Zornitza Stark edited their review of gene: PNPLA6: Changed publications: 25480986, 33818269, 32758583, 30097146; Changed phenotypes: Oliver-McFarlane syndrome, MIM# 275400, Laurence-Moon syndrome, MIM# 245800
Mendeliome v0.8984 PI4KA Zornitza Stark Phenotypes for gene: PI4KA were changed from Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531 to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531; Neurodevelopmental syndrome with hypomyelinating leukodystrophy
Mendeliome v0.8983 PI4KA Zornitza Stark Publications for gene: PI4KA were set to 25855803
Mendeliome v0.8982 PI4KA Zornitza Stark Classified gene: PI4KA as Green List (high evidence)
Mendeliome v0.8982 PI4KA Zornitza Stark Gene: pi4ka has been classified as Green List (High Evidence).
Mendeliome v0.8981 PI4KA Zornitza Stark changed review comment from: Single family reported, aware of at least one other yet to be published family identified internally.; to: PMG: Single family reported, aware of at least one other yet to be published family identified internally.
Mendeliome v0.8981 PI4KA Zornitza Stark edited their review of gene: PI4KA: Added comment: Neurodevelopmental syndrome with hypomyelinating leukodystrophy: 10 unrelated patients harbouring biallelic variants in PI4KA reported with a spectrum of severe global neurodevelopmental delay, hypomyelination, and developmental brain abnormalities, and pure spastic paraplegia. Some patients presented immunological deficits or genito-urinary abnormalities. Western blotting and immunofluorescence showed decreased PI4KA levels in the patients' fibroblasts. Immunofluorescence and targeted lipidomics indicated that PI4KA activity was diminished in fibroblasts and peripheral blood mononuclear cells.; Changed rating: GREEN; Changed publications: 25855803, 34415322; Changed phenotypes: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531, Neurodevelopmental syndrome with hypomyelinating leukodystrophy
Mendeliome v0.8981 NIID Bryony Thompson Marked STR: NIID as ready
Mendeliome v0.8981 NIID Bryony Thompson Str: niid has been classified as Green List (High Evidence).
Mendeliome v0.8981 NIID Bryony Thompson Classified STR: NIID as Green List (high evidence)
Mendeliome v0.8981 NIID Bryony Thompson Str: niid has been classified as Green List (High Evidence).
Mendeliome v0.8980 NIID Bryony Thompson STR: NIID was added
STR: NIID was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: NIID was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: NIID were set to 31178126; 31332381; 31819945; 33887199; 33943039; 32250060; 31332380; 32852534; 32989102; 34333668
Phenotypes for STR: NIID were set to Neuronal intranuclear inclusion disease MIM#603472; Oculopharyngodistal myopathy 3 MIM#619473; Tremor, hereditary essential, 6 MIM#618866
Review for STR: NIID was set to GREEN
STR: NIID was marked as clinically relevant
Added comment: NM_001364012.2:c.-164GGC[X]
Expanded repeat in NOTCH2NLC sequence is (GGC)9(GGA)2(GGC)2.
Large number of families and sporadic cases reported with expansions, with a range of neurodegenerative phenotypes, including: dementia, Parkinsonism/tremor, peripheral neuropathy, leukoencephalopathy, myopathy, motor neurone disease.
Normal repeat range: 4-40, 1 control had 61 repeats and may have been a presymptomatic carrier.
Intermediate range: 41-60 identified in Parkinson's disease
Pathogenic repeat range: >=60-520
Mechanism of disease is translation of repeat expansion into a toxic polyglycine protein, identified in both mouse models and tissue samples from affected individuals.
Sources: Literature
Mendeliome v0.8979 Bryony Thompson removed STR:NIID from the panel
Mendeliome v0.8978 SUCO Bryony Thompson Marked gene: SUCO as ready
Mendeliome v0.8978 SUCO Bryony Thompson Gene: suco has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8978 SUCO Bryony Thompson Classified gene: SUCO as Amber List (moderate evidence)
Mendeliome v0.8978 SUCO Bryony Thompson Gene: suco has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8977 SUCO Bryony Thompson gene: SUCO was added
gene: SUCO was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SUCO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUCO were set to 29620724; 20440000
Phenotypes for gene: SUCO were set to Osteogenesis imperfecta
Review for gene: SUCO was set to AMBER
Added comment: A single case with diffuse osteopenia, multiple fractures with limb deformities, and short long bones, with biallelic variants (a missense and a splice site variant). Also, a null mouse model with acute onset skeletal defects that include impaired bone formation and spontaneous fractures.
Sources: Literature
Mendeliome v0.8976 IGFALS Zornitza Stark Marked gene: IGFALS as ready
Mendeliome v0.8976 IGFALS Zornitza Stark Gene: igfals has been classified as Green List (High Evidence).
Mendeliome v0.8976 IGFALS Zornitza Stark Phenotypes for gene: IGFALS were changed from to Acid-labile subunit, deficiency of, MIM# 615961
Mendeliome v0.8975 IGFALS Zornitza Stark Publications for gene: IGFALS were set to
Mendeliome v0.8974 IGFALS Zornitza Stark Mode of inheritance for gene: IGFALS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8973 IGFALS Zornitza Stark reviewed gene: IGFALS: Rating: GREEN; Mode of pathogenicity: None; Publications: 14762184, 21396577, 34136918; Phenotypes: Acid-labile subunit, deficiency of, MIM# 615961; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8973 FAME1 Bryony Thompson Marked STR: FAME1 as ready
Mendeliome v0.8973 FAME1 Bryony Thompson Str: fame1 has been classified as Green List (High Evidence).
Mendeliome v0.8973 FAME1 Bryony Thompson Classified STR: FAME1 as Green List (high evidence)
Mendeliome v0.8973 FAME1 Bryony Thompson Str: fame1 has been classified as Green List (High Evidence).
Mendeliome v0.8972 FAME1 Bryony Thompson STR: FAME1 was added
STR: FAME1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for STR: FAME1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for STR: FAME1 were set to 30194086; 29507423
Phenotypes for STR: FAME1 were set to Epilepsy, familial adult myoclonic, 1 MIM#601068
Review for STR: FAME1 was set to GREEN
STR: FAME1 was marked as clinically relevant
Added comment: NC_000008.10:g.119379055_119379157TGAAA[X]TAAAA[X]
A heterozygous or homozygous 5-bp expanded TTTCA(n) insertion associated with an upstream 5-bp TTTTA(n) repeat expansion in a noncoding region within intron 4 of the SAMD12 gene, was identified in over 50 Chinese and Japanese families. 4 homozygous cases from 3 families had a more severe phenotype. The TTTTA repeat was present in controls, while the TTTCA was absent and only present in cases (100-3680 repeats reported). RNA toxicity is expected to be the mechanism of disease.
Sources: Expert list
Mendeliome v0.8971 SAMD12 Bryony Thompson Classified gene: SAMD12 as No list
Mendeliome v0.8971 SAMD12 Bryony Thompson Added comment: Comment on list classification: Added as an STR to panel under FAME1.
Mendeliome v0.8971 SAMD12 Bryony Thompson Gene: samd12 has been removed from the panel.
Mendeliome v0.8970 SCA36 Bryony Thompson Publications for STR: SCA36 were set to 25101480
Mendeliome v0.8969 SCA36 Bryony Thompson edited their review of STR: SCA36: Changed publications: 21683323
Mendeliome v0.8969 MYO1H Zornitza Stark Marked gene: MYO1H as ready
Mendeliome v0.8969 MYO1H Zornitza Stark Gene: myo1h has been classified as Red List (Low Evidence).
Mendeliome v0.8969 MYO1H Zornitza Stark gene: MYO1H was added
gene: MYO1H was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYO1H was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYO1H were set to 28779001
Phenotypes for gene: MYO1H were set to Central hypoventilation syndrome, congenital, 2, and autonomic dysfunction, MIM#619482
Review for gene: MYO1H was set to RED
Added comment: Single family reported with three affected children, homozygous LoF variant.
Sources: Literature
Mendeliome v0.8968 BLM Zornitza Stark Marked gene: BLM as ready
Mendeliome v0.8968 BLM Zornitza Stark Gene: blm has been classified as Green List (High Evidence).
Mendeliome v0.8968 BLM Zornitza Stark Phenotypes for gene: BLM were changed from to Bloom Syndrome MIM# 210900; Short stature, dysmorphic facies; sun-sensitive; immunoglobulin deficiency (IgA, IgG, IgM); erythema; marrow failure; leukaemia; lymphoma; chromosomal instability; predisposition to malignancies
Mendeliome v0.8967 BLM Zornitza Stark Publications for gene: BLM were set to
Mendeliome v0.8966 BLM Zornitza Stark Mode of inheritance for gene: BLM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8965 PRKDC Zornitza Stark Marked gene: PRKDC as ready
Mendeliome v0.8965 PRKDC Zornitza Stark Gene: prkdc has been classified as Green List (High Evidence).
Mendeliome v0.8965 PRKDC Zornitza Stark Phenotypes for gene: PRKDC were changed from to Immunodeficiency 26, with or without neurologic abnormalities MIM# 615966; Absent T and B cells; normal NK cells; SCID; recurrent respiratory infections; microcephaly; seizures; developmental delay
Mendeliome v0.8964 PRKDC Zornitza Stark Publications for gene: PRKDC were set to
Mendeliome v0.8963 PRKDC Zornitza Stark Mode of inheritance for gene: PRKDC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8962 PRKDC Zornitza Stark reviewed gene: PRKDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 19075392, 23722905; Phenotypes: Immunodeficiency 26, with or without neurologic abnormalities MIM# 615966, Absent T and B cells, normal NK cells, SCID, recurrent respiratory infections, microcephaly, seizures, developmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8962 TBX1 Zornitza Stark Marked gene: TBX1 as ready
Mendeliome v0.8962 TBX1 Zornitza Stark Gene: tbx1 has been classified as Green List (High Evidence).
Mendeliome v0.8962 TBX1 Zornitza Stark Phenotypes for gene: TBX1 were changed from to DiGeorge syndrome MIM# 188400; Velocardiofacial syndrome MIM# 192430; Decreased T cells; Hypoparathyroidism; Conotruncal cardiac malformation; velopalatal insufficiency; abnormal facies (cleft palate, prominent tubular nose etc); intellectual disability; Immunodeficiency; thymic hypoplasia or aplasia with resultant T‐cell dysfunction; renal anomalies; autoimmunity
Mendeliome v0.8961 TBX1 Zornitza Stark Publications for gene: TBX1 were set to
Mendeliome v0.8960 TBX1 Zornitza Stark Mode of inheritance for gene: TBX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8959 TBX1 Zornitza Stark Tag SV/CNV tag was added to gene: TBX1.
Mendeliome v0.8959 TBX1 Zornitza Stark reviewed gene: TBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301696, 31830774, 16684884; Phenotypes: DiGeorge syndrome MIM# 188400, Velocardiofacial syndrome MIM# 192430, Decreased T cells, Hypoparathyroidism, Conotruncal cardiac malformation, velopalatal insufficiency, abnormal facies (cleft palate, prominent tubular nose etc), intellectual disability, Immunodeficiency, thymic hypoplasia or aplasia with resultant T‐cell dysfunction, renal anomalies, autoimmunity; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8959 RTEL1 Zornitza Stark Marked gene: RTEL1 as ready
Mendeliome v0.8959 RTEL1 Zornitza Stark Gene: rtel1 has been classified as Green List (High Evidence).
Mendeliome v0.8959 RTEL1 Zornitza Stark Phenotypes for gene: RTEL1 were changed from to Dyskeratosis congenita, autosomal dominant 4 MIM# 615190; Dyskeratosis congenita, autosomal recessive 5 MIM# 615190; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 3 MIM# 616373
Mendeliome v0.8958 RTEL1 Zornitza Stark Publications for gene: RTEL1 were set to
Mendeliome v0.8957 RTEL1 Zornitza Stark Mode of inheritance for gene: RTEL1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8956 RTEL1 Zornitza Stark reviewed gene: RTEL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301779, 23329068, 15210109, 23453664, 19461895, 25848748, 25607374; Phenotypes: Dyskeratosis congenita, autosomal dominant 4 MIM# 615190, Dyskeratosis congenita, autosomal recessive 5 MIM# 615190, Pulmonary fibrosis and/or bone marrow failure, telomere-related, 3 MIM# 616373; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8956 RMRP Zornitza Stark changed review comment from: Over 60 pathogenic RMRP variants have been reported resulting in CHH phenotypes; multiple mouse models

Homozygous and Compound heterozygous (insertions, duplications and missense) variants have been reported resulting in loss of function.
*Founder variant g.70A>G (Amish and Finnish populations)

CHH individuals present with variable features that may include: shortened limbs, short stature, metaphysical dysplasia, fine, sparse and/or light-coloured hair, hematologic abnormalities and a spectrum of combined immunodeficiency.; to: Over 60 pathogenic RMRP variants have been reported resulting in CHH phenotypes; multiple mouse models

Homozygous and Compound heterozygous (insertions, duplications and missense) variants have been reported resulting in loss of function.
*Founder variant g.70A>G (Amish and Finnish populations)

CHH individuals present with variable features that may include: shortened limbs, short stature, metaphysical dysplasia, fine, sparse and/or light-coloured hair, hematologic abnormalities and a spectrum of combined immunodeficiency.

Anauxetic dysplasia 1, MIM# 607095 is a more severe phenotype, whereas Metaphyseal dysplasia without hypotrichosis, MIM# 250460 is milder.
Mendeliome v0.8956 RMRP Zornitza Stark edited their review of gene: RMRP: Changed publications: 16244706, 21396580, 22420014, 11940090, 16252239
Mendeliome v0.8956 RMRP Zornitza Stark edited their review of gene: RMRP: Changed phenotypes: Cartilage hair hypoplasia (CHH) MIM#250250, Anauxetic dysplasia 1, MIM# 607095, Metaphyseal dysplasia without hypotrichosis, MIM# 250460
Mendeliome v0.8956 RMRP Zornitza Stark Marked gene: RMRP as ready
Mendeliome v0.8956 RMRP Zornitza Stark Gene: rmrp has been classified as Green List (High Evidence).
Mendeliome v0.8956 RMRP Zornitza Stark Phenotypes for gene: RMRP were changed from to Cartilage-hair hypoplasia MIM#250250
Mendeliome v0.8955 RMRP Zornitza Stark Publications for gene: RMRP were set to
Mendeliome v0.8954 RMRP Zornitza Stark Mode of inheritance for gene: RMRP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8953 RMRP Zornitza Stark reviewed gene: RMRP: Rating: GREEN; Mode of pathogenicity: None; Publications: 16244706, 21396580, 22420014; Phenotypes: Cartilage hair hypoplasia (CHH) MIM#250250, shortened limbs, short stature, metaphysical dysplasia, fine, sparse and/or light-coloured hair, hematologic abnormalities, CID, impaired lymphocyte proliferation, low Ig levels, antibodies variably decreased, bone marrow failure, autoimmunity, susceptibility to lymphoma and other cancers, impaired spermatogenesis, neuronal dysplasia of the intestine; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8953 BLM Danielle Ariti reviewed gene: BLM: Rating: GREEN; Mode of pathogenicity: None; Publications: 17407155, 9285778, 7585968, 8079989, 12242442, 11101838; Phenotypes: Bloom Syndrome MIM# 210900, Short stature, dysmorphic facies, sun-sensitive, immunoglobulin deficiency (IgA, IgG, IgM), erythema, marrow failure, leukaemia, lymphoma, chromosomal instability, predisposition to malignancies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8953 RFX5 Zornitza Stark Marked gene: RFX5 as ready
Mendeliome v0.8953 RFX5 Zornitza Stark Gene: rfx5 has been classified as Green List (High Evidence).
Mendeliome v0.8953 RFX5 Zornitza Stark Phenotypes for gene: RFX5 were changed from to Bare lymphocyte syndrome, type II, complementation group C MIM# 209920; Bare lymphocyte syndrome, type II, complementation group E MIM# 209920
Mendeliome v0.8952 RFX5 Zornitza Stark Publications for gene: RFX5 were set to
Mendeliome v0.8951 RFX5 Zornitza Stark Mode of inheritance for gene: RFX5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8950 RFX5 Zornitza Stark reviewed gene: RFX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 9401005, 29527204, 30170160, 7990905, 8642248, 7699327; Phenotypes: Bare lymphocyte syndrome, type II, complementation group C MIM# 209920, Bare lymphocyte syndrome, type II, complementation group E MIM# 209920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8950 ELMOD3 Zornitza Stark Phenotypes for gene: ELMOD3 were changed from Deafness, autosomal recessive 88, MIM# 615429; Deafness, autosomal dominant to Deafness, autosomal recessive 88, MIM# 615429; Deafness, autosomal dominant 81, MIM# 619500
Mendeliome v0.8949 ELMOD3 Zornitza Stark edited their review of gene: ELMOD3: Changed phenotypes: Deafness, autosomal recessive 88, MIM# 615429, Deafness, autosomal dominant 81, MIM# 619500
Mendeliome v0.8949 TYK2 Zornitza Stark Marked gene: TYK2 as ready
Mendeliome v0.8949 TYK2 Zornitza Stark Gene: tyk2 has been classified as Green List (High Evidence).
Mendeliome v0.8949 TYK2 Zornitza Stark Phenotypes for gene: TYK2 were changed from to Immunodeficiency 35, MIM# 611521
Mendeliome v0.8948 TYK2 Zornitza Stark Publications for gene: TYK2 were set to
Mendeliome v0.8947 TYK2 Zornitza Stark Mode of inheritance for gene: TYK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8946 TYK2 Zornitza Stark reviewed gene: TYK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 17088085, 17521577, 26304966; Phenotypes: Immunodeficiency 35, MIM# 611521; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8946 RAG1 Zornitza Stark Marked gene: RAG1 as ready
Mendeliome v0.8946 RAG1 Zornitza Stark Gene: rag1 has been classified as Green List (High Evidence).
Mendeliome v0.8946 RAG1 Zornitza Stark Phenotypes for gene: RAG1 were changed from to Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity MIM# 609889; Combined cellular and humoral immune defects with granulomas MIM# 233650; Omenn syndrome MIM# 603554; Severe combined immunodeficiency, B cell-negative MIM# 601457
Mendeliome v0.8945 RAG1 Zornitza Stark Publications for gene: RAG1 were set to
Mendeliome v0.8944 RAG1 Zornitza Stark Mode of inheritance for gene: RAG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8943 RAG2 Zornitza Stark Marked gene: RAG2 as ready
Mendeliome v0.8943 RAG2 Zornitza Stark Gene: rag2 has been classified as Green List (High Evidence).
Mendeliome v0.8943 RAG2 Zornitza Stark Phenotypes for gene: RAG2 were changed from to Omenn syndrome MIM# 603554; Severe combined immunodeficiency, B cell-negative MIM# 601457; Combined cellular and humoral immune defects with granulomas MIM# 233650
Mendeliome v0.8942 RAG2 Zornitza Stark Publications for gene: RAG2 were set to
Mendeliome v0.8941 RAG2 Zornitza Stark Mode of inheritance for gene: RAG2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8940 EDEM3 Zornitza Stark Phenotypes for gene: EDEM3 were changed from Congenital disorder of glycosylation; Developmental delay to Congenital disorder of glycosylation, type 2V, MIM# 619493
Mendeliome v0.8939 EDEM3 Zornitza Stark reviewed gene: EDEM3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type 2V, MIM# 619493; Mode of inheritance: None
Mendeliome v0.8939 RAG2 Danielle Ariti reviewed gene: RAG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 9630231, 11313270, 31885011, 8810255, 15025726, 18463379; Phenotypes: Omenn syndrome MIM# 603554, Severe combined immunodeficiency, B cell-negative MIM# 601457, Combined cellular and humoral immune defects with granulomas MIM# 233650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8939 RAC2 Zornitza Stark Marked gene: RAC2 as ready
Mendeliome v0.8939 RAC2 Zornitza Stark Gene: rac2 has been classified as Green List (High Evidence).
Mendeliome v0.8939 RAC2 Zornitza Stark Phenotypes for gene: RAC2 were changed from to Immunodeficiency 73A with defective neutrophil chemotaxix and leukocytosis MIM# 608203; Immunodeficiency 73C with defective neutrophil chemotaxis and hypogammaglobulinaemia MIM# 618987; Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopaenia MIM# 618986
Mendeliome v0.8938 RAC2 Zornitza Stark Publications for gene: RAC2 were set to
Mendeliome v0.8937 RAG1 Danielle Ariti reviewed gene: RAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16276422, 18463379, 20489056, 9630231, 11313270, 17476359, 8810255, 6823332; Phenotypes: Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity MIM# 609889, Combined cellular and humoral immune defects with granulomas MIM# 233650, Omenn syndrome MIM# 603554, Severe combined immunodeficiency, B cell-negative MIM# 601457; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8937 RAC2 Zornitza Stark Mode of pathogenicity for gene: RAC2 was changed from to Other
Mendeliome v0.8936 RAC2 Zornitza Stark Mode of inheritance for gene: RAC2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8935 RAC2 Danielle Ariti reviewed gene: RAC2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 21167572, 10758162, 10072071, 25512081, 32542921, 31919089; Phenotypes: Immunodeficiency 73A with defective neutrophil chemotaxix and leukocytosis MIM# 608203, Immunodeficiency 73C with defective neutrophil chemotaxis and hypogammaglobulinaemia MIM# 618987, Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopaenia MIM# 618986; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8935 MTHFD1 Danielle Ariti reviewed gene: MTHFD1: Rating: GREEN; Mode of pathogenicity: None; Publications: Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinaemia MIM # 617780, Decreased Ig levels, poor antibody responses to conjugated polysaccharide antigens, low B/T/NK cells, Recurrent bacterial infection, megaloblastic anaemia, failure to thrive, neutropenia, seizures, intellectual disability, folate-responsive, Lymphopaenia; Phenotypes: 32414565, 19033438; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8935 GLI2 Zornitza Stark Marked gene: GLI2 as ready
Mendeliome v0.8935 GLI2 Zornitza Stark Gene: gli2 has been classified as Green List (High Evidence).
Mendeliome v0.8935 GLI2 Zornitza Stark Phenotypes for gene: GLI2 were changed from to Culler-Jones syndrome, MIM#615849; Holoprosencephaly 9, MIM# 61082)
Mendeliome v0.8934 GLI2 Zornitza Stark Publications for gene: GLI2 were set to
Mendeliome v0.8933 GLI2 Zornitza Stark Mode of inheritance for gene: GLI2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8932 GLI2 Zornitza Stark changed review comment from: Culler-Jones syndrome (CJS) is characterized by hypopituitarism, mainly growth hormone deficiency, and/or postaxial polydactyly. The phenotype is highly variable, and some individuals may have midline facial defects and developmental delay. The disorder shows incomplete penetrance and variable expressivity. Multiple families reported, short stature is a feature as a result of GH deficiency.

Variants in GLI2 are also associated with HPE, at least 5 families reported. Short stature is observed more rarely, as a result of midline defect.; to: Culler-Jones syndrome (CJS) is characterized by hypopituitarism, mainly growth hormone deficiency, and/or postaxial polydactyly. The phenotype is highly variable, and some individuals may have midline facial defects and developmental delay. The disorder shows incomplete penetrance and variable expressivity. Multiple families reported.

Variants in GLI2 are also associated with HPE, at least 5 families reported.
Mendeliome v0.8932 GLI2 Zornitza Stark reviewed gene: GLI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 14581620, 17096318, 33235745, 27585885, 15994174, 20685856, 30629636, 30583238; Phenotypes: Culler-Jones syndrome, MIM#615849, Holoprosencephaly 9, MIM# 61082); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8932 GHSR Zornitza Stark Marked gene: GHSR as ready
Mendeliome v0.8932 GHSR Zornitza Stark Gene: ghsr has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8932 GHSR Zornitza Stark Phenotypes for gene: GHSR were changed from to Growth hormone deficiency, isolated partial, MIM# 615925
Mendeliome v0.8931 GHSR Zornitza Stark Publications for gene: GHSR were set to
Mendeliome v0.8930 GHSR Zornitza Stark Mode of inheritance for gene: GHSR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8929 GHSR Zornitza Stark Classified gene: GHSR as Amber List (moderate evidence)
Mendeliome v0.8929 GHSR Zornitza Stark Gene: ghsr has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8928 GHSR Zornitza Stark reviewed gene: GHSR: Rating: AMBER; Mode of pathogenicity: None; Publications: 25557026, 19789204, 16511605; Phenotypes: Growth hormone deficiency, isolated partial, MIM# 615925; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8928 PDE6D Zornitza Stark edited their review of gene: PDE6D: Changed publications: 30423442, 24166846
Mendeliome v0.8928 PDE6D Zornitza Stark Classified gene: PDE6D as Green List (high evidence)
Mendeliome v0.8928 PDE6D Zornitza Stark Gene: pde6d has been classified as Green List (High Evidence).
Mendeliome v0.8927 PDE6D Zornitza Stark changed review comment from: Comment when marking as ready: Second family identified in the literature.; to: Comment when marking as ready: Second family identified in the literature. Good functional data.
Mendeliome v0.8927 PDE6D Zornitza Stark edited their review of gene: PDE6D: Changed rating: GREEN
Mendeliome v0.8927 GHRHR Zornitza Stark Marked gene: GHRHR as ready
Mendeliome v0.8927 GHRHR Zornitza Stark Gene: ghrhr has been classified as Green List (High Evidence).
Mendeliome v0.8927 GHRHR Zornitza Stark Phenotypes for gene: GHRHR were changed from to Growth hormone deficiency, isolated, type IV, MIM# 618157
Mendeliome v0.8926 GHRHR Zornitza Stark Publications for gene: GHRHR were set to
Mendeliome v0.8925 GHRHR Zornitza Stark Mode of inheritance for gene: GHRHR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8924 GHRHR Zornitza Stark reviewed gene: GHRHR: Rating: GREEN; Mode of pathogenicity: None; Publications: 8528260, 10084571, 11232012; Phenotypes: Growth hormone deficiency, isolated, type IV, MIM# 618157; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8924 GHR Zornitza Stark Marked gene: GHR as ready
Mendeliome v0.8924 GHR Zornitza Stark Gene: ghr has been classified as Green List (High Evidence).
Mendeliome v0.8924 GHR Zornitza Stark Phenotypes for gene: GHR were changed from to Growth hormone insensitivity, partial, MIM# 604271; Laron dwarfism, MIM# 262500
Mendeliome v0.8923 GHR Zornitza Stark Publications for gene: GHR were set to
Mendeliome v0.8922 GHR Zornitza Stark Mode of inheritance for gene: GHR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8921 GHR Zornitza Stark reviewed gene: GHR: Rating: GREEN; Mode of pathogenicity: None; Publications: 1999489, 8488849, 7565946; Phenotypes: Growth hormone insensitivity, partial, MIM# 604271, Laron dwarfism, MIM# 262500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8921 SCA12 Bryony Thompson Marked STR: SCA12 as ready
Mendeliome v0.8921 SCA12 Bryony Thompson Str: sca12 has been classified as Green List (High Evidence).
Mendeliome v0.8921 SCA12 Bryony Thompson Classified STR: SCA12 as Green List (high evidence)
Mendeliome v0.8921 SCA12 Bryony Thompson Str: sca12 has been classified as Green List (High Evidence).
Mendeliome v0.8920 SCA12 Bryony Thompson STR: SCA12 was added
STR: SCA12 was added to Mendeliome. Sources: Expert list
Mode of inheritance for STR: SCA12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA12 were set to 27864267; 33811808
Phenotypes for STR: SCA12 were set to Spinocerebellar ataxia 12 MIM#604326
Review for STR: SCA12 was set to GREEN
STR: SCA12 was marked as clinically relevant
Added comment: NM_181675.3:c.27CAG[X]
Uncertain if CAG repeat encodes polyglutamine or instead effects expression of specific splice variants of the encoded phosphatase
Normal: ≤32 repeats
Uncertain: ~40-50 repeats have been reported, 43 repeats is the lowest reported in an established affected individual in a family with SCA12
Established pathogenic (used as diagnostic cut-off): ≥51 repeats
Sources: Expert list
Mendeliome v0.8919 RNU7-1 Zornitza Stark Phenotypes for gene: RNU7-1 were changed from Aicardi–Goutières syndrome-like to Aicardi-Goutieres syndrome 9, MIM# 619487
Mendeliome v0.8918 RNU7-1 Zornitza Stark reviewed gene: RNU7-1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 9, MIM# 619487; Mode of inheritance: None
Mendeliome v0.8918 LSM11 Zornitza Stark Phenotypes for gene: LSM11 were changed from type I interferonopathy Aicardi–Goutières syndrome to Aicardi-Goutieres syndrome 8, MIM# 619486
Mendeliome v0.8917 LSM11 Zornitza Stark reviewed gene: LSM11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 8, MIM# 619486; Mode of inheritance: None
Mendeliome v0.8917 WDR11 Zornitza Stark Marked gene: WDR11 as ready
Mendeliome v0.8917 WDR11 Zornitza Stark Gene: wdr11 has been classified as Green List (High Evidence).
Mendeliome v0.8917 WDR11 Zornitza Stark Phenotypes for gene: WDR11 were changed from to Intellectual disability; Hypogonadotropic hypogonadism 14 with or without anosmia MIM #614858
Mendeliome v0.8916 WDR11 Zornitza Stark Publications for gene: WDR11 were set to
Mendeliome v0.8915 WDR11 Zornitza Stark Mode of inheritance for gene: WDR11 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8914 WDR11 Zornitza Stark reviewed gene: WDR11: Rating: GREEN; Mode of pathogenicity: None; Publications: 34413497; Phenotypes: Intellectual disability, Hypogonadotropic hypogonadism 14 with or without anosmia MIM #614858; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8914 Bryony Thompson removed STR:SCA12 from the panel
Mendeliome v0.8913 GH1 Zornitza Stark Marked gene: GH1 as ready
Mendeliome v0.8913 GH1 Zornitza Stark Gene: gh1 has been classified as Green List (High Evidence).
Mendeliome v0.8913 GH1 Zornitza Stark Phenotypes for gene: GH1 were changed from to Growth hormone deficiency, isolated, type IA, MIM# 262400; Growth hormone deficiency, isolated, type II, MIM# 173100; Kowarski syndrome, MIM# 262650
Mendeliome v0.8912 GH1 Zornitza Stark Publications for gene: GH1 were set to
Mendeliome v0.8911 GH1 Zornitza Stark Mode of inheritance for gene: GH1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8910 GH1 Zornitza Stark reviewed gene: GH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 2840669, 1603635, 12655557, 15671105, 8552145, 9276733, 15713716; Phenotypes: Growth hormone deficiency, isolated, type IA, MIM# 262400, Growth hormone deficiency, isolated, type II, MIM# 173100, Kowarski syndrome, MIM# 262650; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8910 EPHX1 Zornitza Stark Marked gene: EPHX1 as ready
Mendeliome v0.8910 EPHX1 Zornitza Stark Gene: ephx1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8910 EPHX1 Zornitza Stark Phenotypes for gene: EPHX1 were changed from to Lipoatrophic diabetes
Mendeliome v0.8909 EPHX1 Zornitza Stark Publications for gene: EPHX1 were set to
Mendeliome v0.8908 EPHX1 Zornitza Stark Mode of inheritance for gene: EPHX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8907 EPHX1 Zornitza Stark Classified gene: EPHX1 as Amber List (moderate evidence)
Mendeliome v0.8907 EPHX1 Zornitza Stark Gene: ephx1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8906 EPHX1 Zornitza Stark reviewed gene: EPHX1: Rating: AMBER; Mode of pathogenicity: None; Publications: 34342583; Phenotypes: Lipoatrophic diabetes; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8906 CREBBP Zornitza Stark Marked gene: CREBBP as ready
Mendeliome v0.8906 CREBBP Zornitza Stark Gene: crebbp has been classified as Green List (High Evidence).
Mendeliome v0.8906 CREBBP Zornitza Stark Phenotypes for gene: CREBBP were changed from to Rubinstein-Taybi syndrome 1, MIM# 180849; Menke-Hennekam syndrome 1, MIM# 618332
Mendeliome v0.8905 ATM Zornitza Stark Phenotypes for gene: ATM were changed from to Ataxia-telangiectasia, MIM# 208900
Mendeliome v0.8904 ATM Zornitza Stark Publications for gene: ATM were set to
Mendeliome v0.8903 ATM Zornitza Stark reviewed gene: ATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 30137827; Phenotypes: Ataxia-telangiectasia, MIM# 208900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8903 RNU4ATAC Zornitza Stark Phenotypes for gene: RNU4ATAC were changed from Microcephalic osteodysplastic primordial dwarfism, type I (MIM# 210710); Roifman syndrome (MIM# 616651); Lowry-Wood syndrome, MIM# 226960 to Microcephalic osteodysplastic primordial dwarfism, type I (MIM# 210710); Roifman syndrome (MIM# 616651); Lowry-Wood syndrome, MIM# 226960
Mendeliome v0.8902 RNU4ATAC Zornitza Stark Phenotypes for gene: RNU4ATAC were changed from Microcephalic osteodysplastic primordial dwarfism, type I (MIM# 210710); Roifman syndrome (MIM# 616651) to Microcephalic osteodysplastic primordial dwarfism, type I (MIM# 210710); Roifman syndrome (MIM# 616651); Lowry-Wood syndrome, MIM# 226960
Mendeliome v0.8901 RNU4ATAC Zornitza Stark Publications for gene: RNU4ATAC were set to 23794361; 26522830; 30455926
Mendeliome v0.8900 RNU4ATAC Zornitza Stark edited their review of gene: RNU4ATAC: Added comment: Lowry-Wood syndrome (LWS) is characterized by multiple epiphyseal dysplasia and microcephaly. Patients exhibit intrauterine growth retardation and short stature, as well as developmental delay and intellectual disability. Retinal degeneration has been reported in some patients.

Four unrelated families reported.

Note features between the three RNU4ATAC-related conditions overlap and they may not represent distinct disorders.; Changed rating: GREEN; Changed publications: 29265708, 12605445; Changed phenotypes: Lowry-Wood syndrome, MIM# 226960; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8900 TRPS1 Zornitza Stark Marked gene: TRPS1 as ready
Mendeliome v0.8900 TRPS1 Zornitza Stark Gene: trps1 has been classified as Green List (High Evidence).
Mendeliome v0.8900 TRPS1 Zornitza Stark Phenotypes for gene: TRPS1 were changed from to Trichorhinophalangeal syndrome, type I, OMIM # 190350; Trichorhinophalangeal syndrome, type III, OMIM # 190351
Mendeliome v0.8899 TRPS1 Zornitza Stark Publications for gene: TRPS1 were set to
Mendeliome v0.8898 TRPS1 Zornitza Stark Mode of inheritance for gene: TRPS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8897 TRPS1 Zornitza Stark reviewed gene: TRPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11112658, 10615131; Phenotypes: Trichorhinophalangeal syndrome, type I, OMIM # 190350, Trichorhinophalangeal syndrome, type III, OMIM # 190351; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8897 FGD1 Zornitza Stark Marked gene: FGD1 as ready
Mendeliome v0.8897 FGD1 Zornitza Stark Gene: fgd1 has been classified as Green List (High Evidence).
Mendeliome v0.8897 FGD1 Zornitza Stark Phenotypes for gene: FGD1 were changed from to Aarskog-Scott syndrome, MIM # 305400; Mental retardation, X-linked syndromic 16, MIM# 305400
Mendeliome v0.8896 FGD1 Zornitza Stark Publications for gene: FGD1 were set to
Mendeliome v0.8895 FGD1 Zornitza Stark Mode of inheritance for gene: FGD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8894 FGD1 Zornitza Stark reviewed gene: FGD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7954831, 20082460; Phenotypes: Aarskog-Scott syndrome, MIM # 305400, Mental retardation, X-linked syndromic 16, MIM# 305400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8894 BRD4 Zornitza Stark Marked gene: BRD4 as ready
Mendeliome v0.8894 BRD4 Zornitza Stark Gene: brd4 has been classified as Green List (High Evidence).
Mendeliome v0.8894 BRD4 Zornitza Stark Phenotypes for gene: BRD4 were changed from to Cornelia de Lange syndrome
Mendeliome v0.8893 BRD4 Zornitza Stark Publications for gene: BRD4 were set to
Mendeliome v0.8892 BRD4 Zornitza Stark Mode of inheritance for gene: BRD4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8891 BRD4 Zornitza Stark reviewed gene: BRD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 29379197, 30302754, 11997514, 34035299; Phenotypes: Cornelia de Lange syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8891 JPH2 Zornitza Stark Phenotypes for gene: JPH2 were changed from Cardiomyopathy, hypertrophic, MIM#613873; dilated cardiomyopathy to Cardiomyopathy, hypertrophic, MIM#613873; Cardiomyopathy, dilated, 2E, MIM# 619492
Mendeliome v0.8890 JPH2 Zornitza Stark edited their review of gene: JPH2: Changed phenotypes: Cardiomyopathy, hypertrophic, MIM#613873, Cardiomyopathy, dilated, 2E, MIM# 619492
Mendeliome v0.8890 ZNF699 Zornitza Stark Marked gene: ZNF699 as ready
Mendeliome v0.8890 ZNF699 Zornitza Stark Gene: znf699 has been classified as Green List (High Evidence).
Mendeliome v0.8890 ZNF699 Zornitza Stark Classified gene: ZNF699 as Green List (high evidence)
Mendeliome v0.8890 ZNF699 Zornitza Stark Gene: znf699 has been classified as Green List (High Evidence).
Mendeliome v0.8889 ZNF699 Zornitza Stark gene: ZNF699 was added
gene: ZNF699 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF699 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF699 were set to 33875846
Phenotypes for gene: ZNF699 were set to DEGCAGS syndrome, MIM# 619488
Review for gene: ZNF699 was set to GREEN
Added comment: DEGCAGS syndrome is a neurodevelopmental disorder characterized by global developmental delay, coarse and dysmorphic facial features, and poor growth and feeding apparent from infancy. Affected individuals have variable systemic manifestations often with significant structural defects of the cardiovascular, genitourinary, gastrointestinal, and/or skeletal systems. Additional features may include sensorineural hearing loss, hypotonia, anaemia or pancytopaenia, and immunodeficiency with recurrent infections.

12 unrelated families reported, 5 different homozygous frameshift variants.
Sources: Literature
Mendeliome v0.8888 SMC1A Zornitza Stark Phenotypes for gene: SMC1A were changed from Cornelia de Lange syndrome 2, MIM# 300590 to Cornelia de Lange syndrome 2, MIM# 300590; Epileptic encephalopathy, early infantile, 85, with or without midline brain defects, MIM# 301044
Mendeliome v0.8887 SMC1A Zornitza Stark Publications for gene: SMC1A were set to 17273969; 22106055; 19701948; 26752331; 28166369
Mendeliome v0.8886 SMC1A Zornitza Stark reviewed gene: SMC1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29023665, 31409060, 31334757, 28166369; Phenotypes: Cornelia de Lange syndrome 2, MIM# 300590, Epileptic encephalopathy, early infantile, 85, with or without midline brain defects, MIM# 301044; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.8886 DCLRE1B Zornitza Stark Marked gene: DCLRE1B as ready
Mendeliome v0.8886 DCLRE1B Zornitza Stark Gene: dclre1b has been classified as Red List (Low Evidence).
Mendeliome v0.8886 DCLRE1B Zornitza Stark Phenotypes for gene: DCLRE1B were changed from to Dyskeratosis congenita and Hoyeraal-Hreidarsson (HH) syndrome
Mendeliome v0.8885 DCLRE1B Zornitza Stark Publications for gene: DCLRE1B were set to
Mendeliome v0.8884 DCLRE1B Zornitza Stark Classified gene: DCLRE1B as Red List (low evidence)
Mendeliome v0.8884 DCLRE1B Zornitza Stark Gene: dclre1b has been classified as Red List (Low Evidence).
Mendeliome v0.8883 DCLRE1B Zornitza Stark reviewed gene: DCLRE1B: Rating: RED; Mode of pathogenicity: None; Publications: 20479256, 21647296; Phenotypes: Dyskeratosis congenita and Hoyeraal-Hreidarsson (HH) syndrome; Mode of inheritance: Unknown
Mendeliome v0.8883 TOR1AIP1 Zornitza Stark Phenotypes for gene: TOR1AIP1 were changed from Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Progeroid appearance; Cataracts; Microcephaly; Deafness; Contractures to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Congenital myasthenic syndrome
Mendeliome v0.8882 TOR1AIP1 Zornitza Stark Publications for gene: TOR1AIP1 were set to 24856141; 31299614; 30723199; 27342937; 32055997
Mendeliome v0.8881 TOR1AIP1 Zornitza Stark edited their review of gene: TOR1AIP1: Added comment: Gene is associated with multiple muscle phenotypes as already noted. Single family myasthenic syndrome and supportive mouse model data.; Changed rating: GREEN; Changed publications: 33215087; Changed phenotypes: Congenital myasthenic syndrome; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8881 PAPPA2 Zornitza Stark Marked gene: PAPPA2 as ready
Mendeliome v0.8881 PAPPA2 Zornitza Stark Gene: pappa2 has been classified as Green List (High Evidence).
Mendeliome v0.8881 PAPPA2 Zornitza Stark Classified gene: PAPPA2 as Green List (high evidence)
Mendeliome v0.8881 PAPPA2 Zornitza Stark Gene: pappa2 has been classified as Green List (High Evidence).
Mendeliome v0.8880 PAPPA2 Zornitza Stark gene: PAPPA2 was added
gene: PAPPA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PAPPA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAPPA2 were set to 26902202; 34272725; 32739295
Phenotypes for gene: PAPPA2 were set to Short stature, Dauber-Argente type, MIM#619489
Review for gene: PAPPA2 was set to GREEN
Added comment: Short stature of the Dauber-Argente type (SSDA) is characterized by progressive postnatal growth failure, moderate microcephaly, thin long bones, and mildly decreased bone density. Patients have elevated circulating levels of total IGF1 due to impaired proteolysis of IGFBP3 and IGFBP5, resulting in reduced free IGF1.

7 individuals from 3 unrelated families reported, mouse model.
Sources: Literature
Mendeliome v0.8879 ATR Zornitza Stark Marked gene: ATR as ready
Mendeliome v0.8879 ATR Zornitza Stark Gene: atr has been classified as Green List (High Evidence).
Mendeliome v0.8879 ATR Zornitza Stark Phenotypes for gene: ATR were changed from to Seckel syndrome 1, MIM# 210600
Mendeliome v0.8878 ATR Zornitza Stark Publications for gene: ATR were set to
Mendeliome v0.8877 ATR Zornitza Stark Mode of inheritance for gene: ATR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8876 ATR Zornitza Stark reviewed gene: ATR: Rating: GREEN; Mode of pathogenicity: None; Publications: 12640452, 19620979, 30199583, 23111928; Phenotypes: Seckel syndrome 1, MIM# 210600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8876 SHOX Zornitza Stark Marked gene: SHOX as ready
Mendeliome v0.8876 SHOX Zornitza Stark Gene: shox has been classified as Green List (High Evidence).
Mendeliome v0.8876 SHOX Zornitza Stark Phenotypes for gene: SHOX were changed from to Langer mesomelic dysplasia, MIM# 249700; Leri-Weill dyschondrosteosis, MIM# 127300
Mendeliome v0.8875 SHOX Zornitza Stark Mode of inheritance for gene: SHOX was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8874 SHOX Zornitza Stark Tag SV/CNV tag was added to gene: SHOX.
Mendeliome v0.8874 SHOX Zornitza Stark reviewed gene: SHOX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Langer mesomelic dysplasia, MIM# 249700, Leri-Weill dyschondrosteosis, MIM# 127300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8874 ORC4 Zornitza Stark Marked gene: ORC4 as ready
Mendeliome v0.8874 ORC4 Zornitza Stark Gene: orc4 has been classified as Green List (High Evidence).
Mendeliome v0.8874 ORC4 Zornitza Stark Phenotypes for gene: ORC4 were changed from to Meier-Gorlin syndrome 2, MIM# 613800
Mendeliome v0.8873 ORC4 Zornitza Stark Publications for gene: ORC4 were set to
Mendeliome v0.8872 ORC4 Zornitza Stark Mode of inheritance for gene: ORC4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8871 ORC4 Zornitza Stark reviewed gene: ORC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 21358632, 21358631, 23023959, 22333897; Phenotypes: Meier-Gorlin syndrome 2, MIM# 613800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8871 ORC1 Zornitza Stark Marked gene: ORC1 as ready
Mendeliome v0.8871 ORC1 Zornitza Stark Gene: orc1 has been classified as Green List (High Evidence).
Mendeliome v0.8871 ORC1 Zornitza Stark Phenotypes for gene: ORC1 were changed from to Meier-Gorlin syndrome 1, MIM# 224690; MONDO:0009143
Mendeliome v0.8870 ORC1 Zornitza Stark Publications for gene: ORC1 were set to
Mendeliome v0.8869 ORC1 Zornitza Stark Mode of inheritance for gene: ORC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8868 ORC1 Zornitza Stark reviewed gene: ORC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21358633, 21358632, 21358631, 23023959; Phenotypes: Meier-Gorlin syndrome 1, MIM# 224690, MONDO:0009143; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8868 ORC6 Zornitza Stark Marked gene: ORC6 as ready
Mendeliome v0.8868 ORC6 Zornitza Stark Gene: orc6 has been classified as Green List (High Evidence).
Mendeliome v0.8868 ORC6 Zornitza Stark Phenotypes for gene: ORC6 were changed from to Meier-Gorlin syndrome 3, MIM# 613803
Mendeliome v0.8867 ORC6 Zornitza Stark Publications for gene: ORC6 were set to
Mendeliome v0.8866 ORC6 Zornitza Stark Mode of inheritance for gene: ORC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8865 ORC6 Zornitza Stark reviewed gene: ORC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 21358632, 22333897, 25691413, 26139588; Phenotypes: Meier-Gorlin syndrome 3, MIM# 613803; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8865 IGF1 Zornitza Stark Marked gene: IGF1 as ready
Mendeliome v0.8865 IGF1 Zornitza Stark Gene: igf1 has been classified as Green List (High Evidence).
Mendeliome v0.8865 IGF1 Zornitza Stark Phenotypes for gene: IGF1 were changed from to Growth retardation with deafness and mental retardation due to IGF1 deficiency, MIM # 608747
Mendeliome v0.8864 IGF1 Zornitza Stark Publications for gene: IGF1 were set to
Mendeliome v0.8863 IGF1 Zornitza Stark Mode of inheritance for gene: IGF1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8862 IGF1 Zornitza Stark reviewed gene: IGF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8857020, 15769976, 14684690, 31539878, 28768959, 34125705, 22832530; Phenotypes: Growth retardation with deafness and mental retardation due to IGF1 deficiency, MIM # 608747; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8862 IGF2 Zornitza Stark Mode of inheritance for gene: IGF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Mendeliome v0.8861 IGF2 Zornitza Stark changed review comment from: RSS phenotype.; to: Silver-Russell syndrome-3 (SRS3) is characterized by intrauterine growth retardation with relative macrocephaly, followed by feeding difficulties and postnatal growth restriction. Dysmorphic facial features include triangular face, prominent forehead, and low-set ears. Other variable features include limb defects, genitourinary and cardiovascular anomalies, hearing impairment, and developmental delay. Disruption of any gene in the HMGA2-PLAG1-IGF2 pathway results in a decrease in IGF2 expression and produces an SRS phenotype similar to that of patients carrying 11p15.5 epigenetic defects.

Begemann et al. (2015) performed exome sequencing in 4 affected people with severe growth restriction in one family, and identified a heterozygous nonsense mutation in the IGF2 gene that segregated fully with the disorder. Affected individuals inherited the mutation from their healthy fathers, and it originated from the healthy paternal grandmother. Clinical features occurred only in those who inherited the variant allele through paternal transmission, consistent with maternal imprinting of IGF2.

Many other cases reported since with de novo mutations in IGF2 present on the paternal allele.
Mendeliome v0.8861 IGF2 Zornitza Stark edited their review of gene: IGF2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Mendeliome v0.8861 OBSL1 Zornitza Stark Marked gene: OBSL1 as ready
Mendeliome v0.8861 OBSL1 Zornitza Stark Gene: obsl1 has been classified as Green List (High Evidence).
Mendeliome v0.8861 OBSL1 Zornitza Stark Phenotypes for gene: OBSL1 were changed from to 3-M syndrome 2, MIM #612921
Mendeliome v0.8860 OBSL1 Zornitza Stark Publications for gene: OBSL1 were set to
Mendeliome v0.8859 OBSL1 Zornitza Stark Mode of inheritance for gene: OBSL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8858 OBSL1 Zornitza Stark reviewed gene: OBSL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21737058, 19481195, 23018678, 19877176; Phenotypes: 3-M syndrome 2, MIM #612921; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8858 PIK3R1 Zornitza Stark Marked gene: PIK3R1 as ready
Mendeliome v0.8858 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Green List (High Evidence).
Mendeliome v0.8858 PIK3R1 Zornitza Stark Phenotypes for gene: PIK3R1 were changed from to SHORT syndrome, MIM # 269880; Immunodeficiency 36, MIM#616005
Mendeliome v0.8857 PIK3R1 Zornitza Stark Publications for gene: PIK3R1 were set to
Mendeliome v0.8856 PIK3R1 Zornitza Stark Mode of inheritance for gene: PIK3R1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8855 PIK3R1 Zornitza Stark reviewed gene: PIK3R1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23810378, 23810379, 23810382; Phenotypes: SHORT syndrome, MIM # 269880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8855 PLAG1 Zornitza Stark Publications for gene: PLAG1 were set to 28796236; 29913240
Mendeliome v0.8854 PLAG1 Zornitza Stark Classified gene: PLAG1 as Green List (high evidence)
Mendeliome v0.8854 PLAG1 Zornitza Stark Gene: plag1 has been classified as Green List (High Evidence).
Mendeliome v0.8853 PLAG1 Zornitza Stark edited their review of gene: PLAG1: Added comment: Additional families reported, upgrade to Green.

Silver-Russell syndrome-4 (SRS4) is characterised by intrauterine growth retardation followed by feeding difficulties and postnatal growth restriction. Dysmorphic facial features include triangular face and prominent forehead, and relative macrocephaly at birth may be observed. So far 4 families have been reported with some functional studies of the role of the gene in the growth pathway.

Abi Habib et al. (2018) reported 1 family (child, sister and mother) patient with Silver-Russell syndrome (with normal methylation on chromosomes 7, 11, and 14, and exclusion of maternal UPD and chromosomal rearrangements). Using WES they identified a heterozygous 1-bp deletion in the PLAG1 gene. The variant segregated with disease, and was not present in polymorphism databases or ExAC. They also reported another patient with a different heterozygous 1-bp deletion in the PLAG1 gene. This was not found in her unaffected twin brother, older brother, or parents. Experiments in Hep3b cells demonstrated that PLAG1 positively regulates expression of the IGF2 promoter P3, independently and via the HMGA2-PLAG1-IGF2 pathway. Disruption of any gene in the pathway results in a decrease in IGF2 expression and produces an SRS phenotype similar to that of patients carrying 11p15.5 epigenetic defects (SRS1; 180860), except for body asymmetry, which is not expected to occur since the molecular defects are present in all cells of the body, unlike the mosaic epigenetic changes at the 11p15.5 locus.

Inoue et al. (2020) reported 1 family with 2 affected people with Silver-Russell syndrome with a nonsense variant in the PLAG1 gene, which segregated with disease.

Vado et al. (2020) reported 1 family with multiple affected people with Silver-Russell syndrome with a frameshift variant in the PLAG1 gene, which segregated with disease.; Changed rating: GREEN; Changed publications: 28796236, 29913240, 33291420, 32546215
Mendeliome v0.8853 PACRG Zornitza Stark Marked gene: PACRG as ready
Mendeliome v0.8853 PACRG Zornitza Stark Gene: pacrg has been classified as Red List (Low Evidence).
Mendeliome v0.8853 PACRG Zornitza Stark Publications for gene: PACRG were set to
Mendeliome v0.8852 PACRG Zornitza Stark Classified gene: PACRG as Red List (low evidence)
Mendeliome v0.8852 PACRG Zornitza Stark Gene: pacrg has been classified as Red List (Low Evidence).
Mendeliome v0.8851 PACRG Zornitza Stark reviewed gene: PACRG: Rating: RED; Mode of pathogenicity: None; Publications: 31116684, 31182890, 14737177, 27193298; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.8851 WIPF1 Zornitza Stark Marked gene: WIPF1 as ready
Mendeliome v0.8851 WIPF1 Zornitza Stark Gene: wipf1 has been classified as Green List (High Evidence).
Mendeliome v0.8851 WIPF1 Zornitza Stark Phenotypes for gene: WIPF1 were changed from to Wiskott-Aldrich syndrome 2 MIM# 614493; Reduced T cells; defective lymphocyte responses to anti-CD3; high IgE; Thrombocytopenia with or without small platelets; recurrent bacterial and viral Infections; eczema; bloody diarrhoea; gastrointestinal bleeding; WAS protein absent
Mendeliome v0.8850 WIPF1 Zornitza Stark Publications for gene: WIPF1 were set to
Mendeliome v0.8849 WIPF1 Zornitza Stark Mode of inheritance for gene: WIPF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8848 TCN2 Zornitza Stark changed review comment from: Well established gene-disease association.

26 pathogenic TCN2 variants have been reported in over 40 individuals; multiple mouse models

Homologous and Compound Heterozygous TCN2 variants (deletions or insertions, nonsense mutations, and point mutations) have been reported; deletions or insertions are the most common, causing frameshifts that result in protein truncation.

Individuals usually present within the first year of life with failure to thrive, diarrhoea, anaemia, pallor and agammaglobulinaemia.
Sources: Expert list; to: Well established gene-disease association.

26 pathogenic TCN2 variants have been reported in over 40 individuals; multiple mouse models

Homozygous and Compound Heterozygous TCN2 variants (deletions or insertions, nonsense mutations, and point mutations) have been reported; deletions or insertions are the most common, causing frameshifts that result in protein truncation.

Individuals usually present within the first year of life with failure to thrive, diarrhoea, anaemia, pallor and agammaglobulinaemia.
Sources: Expert list
Mendeliome v0.8848 TCN2 Zornitza Stark Marked gene: TCN2 as ready
Mendeliome v0.8848 TCN2 Zornitza Stark Gene: tcn2 has been classified as Green List (High Evidence).
Mendeliome v0.8848 TCN2 Zornitza Stark Publications for gene: TCN2 were set to 19373259
Mendeliome v0.8847 TCN2 Zornitza Stark edited their review of gene: TCN2: Changed publications: 19373259, 32841161, 33023511, 30124850
Mendeliome v0.8847 TCN2 Zornitza Stark changed review comment from: Well established gene-disease association.
Sources: Expert list; to: Well established gene-disease association.

26 pathogenic TCN2 variants have been reported in over 40 individuals; multiple mouse models

Homologous and Compound Heterozygous TCN2 variants (deletions or insertions, nonsense mutations, and point mutations) have been reported; deletions or insertions are the most common, causing frameshifts that result in protein truncation.

Individuals usually present within the first year of life with failure to thrive, diarrhoea, anaemia, pallor and agammaglobulinaemia.
Sources: Expert list
Mendeliome v0.8847 TCN2 Zornitza Stark Phenotypes for gene: TCN2 were changed from to Transcobalamin II deficiency, 275350
Mendeliome v0.8846 TCN2 Zornitza Stark Publications for gene: TCN2 were set to
Mendeliome v0.8845 TCN2 Zornitza Stark Mode of inheritance for gene: TCN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8844 TAP2 Zornitza Stark Marked gene: TAP2 as ready
Mendeliome v0.8844 TAP2 Zornitza Stark Gene: tap2 has been classified as Green List (High Evidence).
Mendeliome v0.8844 TAP2 Zornitza Stark Phenotypes for gene: TAP2 were changed from to Bare lymphocyte syndrome, type I, due to TAP2 deficiency MIM# 604571; Low CD8; absent MHC I on lymphocytes; Vasculitis; pyoderma gangrenosum; recurrent bacterial/viral respiratory infections; bronchiectasis
Mendeliome v0.8843 TAP2 Zornitza Stark Publications for gene: TAP2 were set to
Mendeliome v0.8842 TAP2 Zornitza Stark Mode of inheritance for gene: TAP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8841 TAP1 Zornitza Stark Marked gene: TAP1 as ready
Mendeliome v0.8841 TAP1 Zornitza Stark Gene: tap1 has been classified as Green List (High Evidence).
Mendeliome v0.8841 TAP1 Zornitza Stark Phenotypes for gene: TAP1 were changed from to Bare lymphocyte syndrome, type I MIM#604571; Low CD8; absent MHC I on lymphocytes; vasculitis; pyoderma gangrenosum; skin lesions; recurrent respiratory tract infections; bronchiectasis
Mendeliome v0.8840 TAP1 Zornitza Stark Publications for gene: TAP1 were set to
Mendeliome v0.8839 TAP1 Zornitza Stark Mode of inheritance for gene: TAP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8838 PGRMC1 Bryony Thompson Phenotypes for gene: PGRMC1 were changed from Premature ovarian failure to Premature ovarian failure; Isolated paediatric cataract
Mendeliome v0.8837 PGRMC1 Bryony Thompson Tag SV/CNV tag was added to gene: PGRMC1.
Mendeliome v0.8837 PGRMC1 Bryony Thompson Publications for gene: PGRMC1 were set to 25246111; 18782852
Mendeliome v0.8836 WIPF1 Danielle Ariti reviewed gene: WIPF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22231303, 27742395, 11869681, 14757742; Phenotypes: Wiskott-Aldrich syndrome 2 MIM# 614493, Reduced T cells, defective lymphocyte responses to anti-CD3, high IgE, Thrombocytopenia with or without small platelets, recurrent bacterial and viral Infections, eczema, bloody diarrhoea, gastrointestinal bleeding, WAS protein absent; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8836 PGRMC1 Bryony Thompson Classified gene: PGRMC1 as Amber List (moderate evidence)
Mendeliome v0.8836 PGRMC1 Bryony Thompson Gene: pgrmc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8835 PGRMC1 Bryony Thompson reviewed gene: PGRMC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 33867527, 23783460; Phenotypes: Isolated paediatric cataract; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8835 TAP2 Danielle Ariti reviewed gene: TAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 7517574, 9232449, 10560675, 27861817; Phenotypes: Bare lymphocyte syndrome, type I, due to TAP2 deficiency MIM# 604571, Low CD8, absent MHC I on lymphocytes, Vasculitis, pyoderma gangrenosum, recurrent bacterial/viral respiratory infections, bronchiectasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8835 TAP1 Danielle Ariti reviewed gene: TAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28161407, 10074494, 1473153; Phenotypes: Bare lymphocyte syndrome, type I MIM#604571, Low CD8, absent MHC I on lymphocytes, vasculitis, pyoderma gangrenosum, skin lesions, recurrent respiratory tract infections, bronchiectasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8835 ALS2 Teresa Zhao gene: ALS2 was added
gene: ALS2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ALS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALS2 were set to PMID: 30128655; 33409823
Phenotypes for gene: ALS2 were set to Infantile onset ascending spastic paralysis (MIM#607225); Juvenile amyotrophic lateral sclerosis 2 (MIM#205100); Juvenile primary lateral sclerosis (MIM#606353)
Review for gene: ALS2 was set to GREEN
Added comment: >50 variants reported in multiple individuals with Infantile onset ascending spastic paralysis, mostly originated from the Middle East and Mediterranean countries.
Sources: Literature
Mendeliome v0.8835 RNF220 Zornitza Stark Tag founder tag was added to gene: RNF220.
Mendeliome v0.8835 RNF220 Zornitza Stark Marked gene: RNF220 as ready
Mendeliome v0.8835 RNF220 Zornitza Stark Gene: rnf220 has been classified as Green List (High Evidence).
Mendeliome v0.8835 RNF220 Zornitza Stark Classified gene: RNF220 as Green List (high evidence)
Mendeliome v0.8835 RNF220 Zornitza Stark Gene: rnf220 has been classified as Green List (High Evidence).
Mendeliome v0.8834 RNF220 Zornitza Stark gene: RNF220 was added
gene: RNF220 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNF220 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNF220 were set to 33964137; 10881263
Phenotypes for gene: RNF220 were set to Leukodystrophy; CNS hypomyelination; Ataxia; Intellectual disability; Sensorineural hearing impairment; Elevated hepatic transaminases; Hepatic fibrosis; Dilated cardiomyopathy; Spastic paraplegia; Dysarthria; Abnormality of the corpus callosum
Review for gene: RNF220 was set to GREEN
Added comment: Sferra et al (2021 - PMID: 33964137) provide extensive evidence that biallelic RNF220 mutations cause a disorder characterized by hypomyelinating leukodystrophy, ataxia (9/9 - onset 1-5y), borderline intellectual functioning (3/9) / intellectual disability (5/9 - in most cases mild), sensorineural deafness (9/9) with complete hearing loss in the first decade of life, hepatopathy (9/9) with associated periportal fibrosis, and dilated cardiomyopathy (9/9) which was fatal.

Other neurologic manifestations apart from ataxia incl. hyperreflexia (8/8), spastic paraplegia (9/9), dysarthria (9/9), peripheral neuropathy (4/9), seizures in one case (1/9). Upon brain MRI there was thin corpus callosum (9/9) or cerebellar atrophy in some (2/9).

The authors identified homozygosity for 2 recurrent missense RNF220 variants in affected members belonging to these 5 broad consanguineous pedigrees (7 families), namely NM_018150.4:c.1094G>A / p.Arg365Gly in 4 Roma families in the context of a shared haplotype (/founder effect) as well as c.1088G>A / p.Arg363Gly in a large pedigree from southern Italy initially reported by Leuzzi et al (2000 - PMID: 10881263).

Extensive segregation analyses were carried out including several affected and unaffected members.

RNF220 encodes ring finger protein 220, which functions as an E3 ubiquitin ligase. Previous studies have shown among others a role in modulation of Sonic hedgehog/GLI signaling and cerebellar development

Evidence for the role of RNF220 included relevant expression, localization within the cell, interaction partners (lamin B1, 20S proteasome), similarities with other laminopathies in terms of phenotype, etc :
*RNF220 has a relevant expression pattern in CNS (based on qRT-PCR analyses in human brain, cerebellum, cerebral cortex / mRNA levels in human fetal CNS with higher expression in cerebellum, spinal cord and cortex / previous GTEx data / protein levels in mouse CNS)
*The protein displays nuclear localization based on iPSC cells differentiated to motor neurons (also supported by data from the Human Protein Atlas). Transfection of COS-1 cells demonstrated localization primarily to the nucleus (as also previously demonstrated in HEK293T cells) in vesicle like structures with ASF2/SF2 colocalization suggesting enrichment in nuclear speckles. There was also partial co-distribution with the 20S proteasome. R363Q and R365Q additionally coalesced in the cytoplasm forming protein aggregates/inclusions.
*Immunofluorescence studies in patient fibroblasts also confirmed abnormal increase of the protein in the cytoplasm and increased fluorescence with the 20S proteasome.
*Proteomic identification of RNF220-interacting proteins in transfected HEK293T cells demonstrated enrichment for all members of the lamin protein family (incl . lamin B1, AC, B2).
*RNAi-mediated downregulation of RNF222 in Drosophila suggested altered subcellular localization and accumulation of the fly orthologue for human lamin B1.
*Immunoprecipitation of lamin B1 from the nuclear matrix of cerebellar cells suggested significant interaction of endogenous lamin B1 with RNF220, while transfection studies in HEK293T cells for wt/mt suggested reduced binding to endogenous lamin B1 for RNF220 mt compared to wt (more prominent for R365Q). RNF220 mutants also reduced ubiquitination of nuclear lamin B1 compared to wt.
*Patient fibroblasts immunostained with different nuclear envelope markers displayed abnormal nuclear shapes with multiple invaginations and lobulations, findings also observed in laminopathies.
Sources: Literature
Mendeliome v0.8833 NBAS Zornitza Stark Marked gene: NBAS as ready
Mendeliome v0.8833 NBAS Zornitza Stark Gene: nbas has been classified as Green List (High Evidence).
Mendeliome v0.8833 NBAS Zornitza Stark Phenotypes for gene: NBAS were changed from to Short stature, optic nerve atrophy, and Pelger-Huet anomaly, MIM# 614800; Infantile liver failure syndrome 2, MIM# 616483
Mendeliome v0.8832 NBAS Zornitza Stark Publications for gene: NBAS were set to
Mendeliome v0.8831 NBAS Zornitza Stark Mode of inheritance for gene: NBAS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8830 NBAS Zornitza Stark reviewed gene: NBAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31761904; Phenotypes: Short stature, optic nerve atrophy, and Pelger-Huet anomaly, MIM# 614800, Infantile liver failure syndrome 2, MIM# 616483; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8830 ARF3 Zornitza Stark Marked gene: ARF3 as ready
Mendeliome v0.8830 ARF3 Zornitza Stark Gene: arf3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8830 ARF3 Zornitza Stark Classified gene: ARF3 as Amber List (moderate evidence)
Mendeliome v0.8830 ARF3 Zornitza Stark Gene: arf3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8829 ARF3 Zornitza Stark gene: ARF3 was added
gene: ARF3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARF3 were set to 34346499
Phenotypes for gene: ARF3 were set to Global developmental delay; Intellectual disability; Seizures; Morphological abnormality of the central nervous system
Review for gene: ARF3 was set to AMBER
Added comment: Sakamoto et al (2021 - PMID: 34346499) provide some evidence that monoallelic ARF3 pathogenic variants may be associated with a NDD with brain abnormality.

Using trio exome sequencing, the authors identified 2 individuals with NDD harboring de novo ARF3 variants, namely: NM_001659.2:c.200A>T / p.Asp67Val and c.296G>T / p.Arg99Leu.

Individual 1 (with Asp67Val / age : 4y10m), appeared to be more severelely affected with prenatal onset progressive microcephaly, severe global DD, epilepsy. Upon MRI there was cerebellar and brainstem atrophy. Individual 2 (Arg99Leu / 14y) had severe DD and ID (IQ of 23), epilepsy and upon MRI cerebellar hypoplasia. This subject did not exhibit microcephaly. Common facial features incl. broad nose, full cheeks, small philtrum, strabismus, thin upper lips and abnormal jaw. There was no evidence of systemic involvement in both.

ARF3 encodes ADP-ribosylation factor 3. Adenosine diphosphate ribosylation factors (ARFs) are key proteins for regulation of cargo sorting at the Golgi network, with ARF3 mainly working at the trans-Golgi network. ARFs belong to the small GTP-binding protein (G protein) superfamily. ARF3 switches between an active GTP-bound form and an inactive GDP-bound form, regulated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) respectively.

Members of the ARF superfamily regulate various aspects of membrane traffic, among others in neurons.

There are 5 homologs of ARF families, divided in 3 classes. ARF3 and ARF1 belong to class I. Monoallelic ARF1 mutations are associated with Periventricular nodular heterotopia 8 (MIM 618185).

In vivo, in vitro and in silico studies for the 2 variants suggest that both impair the Golgi transport system although each variant most likely exerts a different effect (gain-of-function for Arg99Leu vs loss-of-function/dominant-negative for Asp67Val).

This was also reflected in somewhat different phenotype of the subjects with the respective variants. Common features included severe DD, epilepsy and brain abnormalities although Asp67Val was associated with diffuse brain atrophy as well as congenital microcephaly and Arg99Leu with cerebellar hypoplasia.

Evidence to support the effect of each variant include:

Arg99Leu:
Had identical Golgi localization to that of wt
Had increased binding activity with GGA1, a protein recruited by the GTP-bound active form of ARF3 to the TGN membrane (supporting GoF)
In silico structural analysis suggested it may fail to stabilize the conformation of Asp26, resulting in impaired GTP hydrolysis (GoF).
In transgenic fruit flies, evaluation of the ARF3 variant toxicity using the rough eye phenotype this variant was associated with increased severity of the r-e phenotype similar to a previously studied GoF variant (Gln71Leu)

Asp67Val:
Did not show a Golgi-like pattern of localization (similar to Thr31Asn a previously studied dominant-negative variant)
Displayed decreased protein stability
In silico structural analysis suggested that Asp67Val may lead to compromised binding of GTP or GDP (suggestive of LoF)
In transgenic Drosophila eye-specific expression of Asp67Val (similar to Thr31Asn, a known dominant-negative variant) was lethal possibly due to high toxicity in very small amounts in tissues outside the eye.

There is no associated phenotype in OMIM, G2P or SysID.
Sources: Literature
Mendeliome v0.8828 CEP57 Zornitza Stark Marked gene: CEP57 as ready
Mendeliome v0.8828 CEP57 Zornitza Stark Gene: cep57 has been classified as Green List (High Evidence).
Mendeliome v0.8828 CEP57 Zornitza Stark Phenotypes for gene: CEP57 were changed from to Mosaic variegated aneuploidy syndrome 2, #MIM 614114
Mendeliome v0.8827 CEP57 Zornitza Stark Publications for gene: CEP57 were set to
Mendeliome v0.8826 CEP57 Zornitza Stark Mode of inheritance for gene: CEP57 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8825 CEP57 Zornitza Stark reviewed gene: CEP57: Rating: GREEN; Mode of pathogenicity: None; Publications: 24259107, 21552266, 32861809, 30147898; Phenotypes: Mosaic variegated aneuploidy syndrome 2, #MIM 614114; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8825 PLXNA2 Zornitza Stark Marked gene: PLXNA2 as ready
Mendeliome v0.8825 PLXNA2 Zornitza Stark Gene: plxna2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8825 PLXNA2 Zornitza Stark Classified gene: PLXNA2 as Amber List (moderate evidence)
Mendeliome v0.8825 PLXNA2 Zornitza Stark Gene: plxna2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8824 PLXNA2 Zornitza Stark gene: PLXNA2 was added
gene: PLXNA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLXNA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNA2 were set to 34327814
Phenotypes for gene: PLXNA2 were set to Intellectual disability; Abnormality of the face; Failure to thrive; Abnormal heart morphology
Review for gene: PLXNA2 was set to AMBER
Added comment: Altuame et al (2021 - PMID: 34327814) describe 3 individuals from 2 consanguineous Arab families with biallelic PLXNA2 variants.

The index patient from the 1st family presented with CHD (hypoplastic right ventricle, ASD), DD and moderate ID (IQ of 40), failure to thrive as well as some dysmorphic features (obtuse mandibular angle, mild overbite, synophrys with downslanting p-f, strabismus, etc). There were additional features (eg. postaxial polydactyly) which were found in other affected and unaffected family members.

Exome sequencing with autozygome analysis revealed homozygosity for a PLXNA2 stopgain variant (NM_025179:c.3603C>A / p.(Cys1201*)).

Sanger confirmation was carried out and segregation analyses confirmed carrier status of the unaffected parents and a sib as well as a brother homozygous for the same variant. Clinical evaluation of the latter, following this finding revealed borderline intellectual functioning, ADHD, failure to thrive. There was no mandibular anomaly or overbite and no clinical evidence of CHD (no echo performed).

The index patient from the 2nd consanguineous family was evaluated for ID (IQ of 63), with previous borderline motor development, ADHD and some dysmorphic features (obtuse mandibular angle and overbite). There was no clinical evidence of CHD (no echo performed).

Exome sequencing with autozygosity mapping revealed a homozygous missense PLXNA2 variant (c.3073G>A / p.(Asp1025Asn), present only once in gnomAD (htz), with rather non-concordant in silico predictions SIFT 0.22, PolyPhen 0.682 and CADD 23.5. The aa was however highly conserved.

Segregation analysis confirmed carrier state of the parents and 2 unaffected sibs, with a 3rd sib homozygous for the wt allele.

As the authors discuss:
*PLXNA2 belongs to the plexin family of genes, encoding transmbembrane proteins functioning as semaphorin receptors. It has predominant expression in neural tissue. The protein is thought to bind semaphorin-3A, -3C or -5 followed by plexin A2 dimerization, activation of its GTPase-activating protein domain, negative regulation of Rap1B GTPase and initiation of a signal transduction cascade mediating axonal repulsion/guidance, dendritic guidance, neuronal migration.
*Murine Plxna2 knockout models display structural brain defects. In addition they display congenital heart defects incl. persistent truncus arteriosus and interrupted aortic arch.
*Rare CNVs in adult humans with tetralogy of Fallot have suggested a potential role of PLXNA2 in cardiac development and CHD.
*Expression and the role of PLXNA2 in human chondrocytes as well as a GWAS in 240 japanese patients with mandibular prognathism where PLXNA2 was suggested as a susceptibility locus.

Overall, the authors recognize some common features (as for cognitive functioning, some dysmorphic features incl. obtuse mandibular angle and overbite in 2 unrelated subjects, failure to thrive 3/3) and provide plausible explanations for the variability / discordance of others eg:
- Cyanotic heart disease explaining discordance in cognitive outcome among sibs
- Incomplete penetrance for CHD (and/or ID or mandibular anomaly) as for few AR disorders and/or
- Additional pathogenic variants possibly explaining the CHD in the first subject.

There is no associated phenotype in OMIM or G2P. SysID includes PLXNA2 among the candidate ID genes.
Sources: Literature
Mendeliome v0.8823 SLC51A Zornitza Stark Marked gene: SLC51A as ready
Mendeliome v0.8823 SLC51A Zornitza Stark Gene: slc51a has been classified as Red List (Low Evidence).
Mendeliome v0.8823 SLC51A Zornitza Stark gene: SLC51A was added
gene: SLC51A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC51A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC51A were set to 31863603
Phenotypes for gene: SLC51A were set to Cholestasis, progressive familial intrahepatic, 6, MIM# 619484
Review for gene: SLC51A was set to RED
Added comment: Single individual reported with homozygous LoF variant, who presented with chronic malabsorptive diarrhoea, easy bruising, episodes of prolonged bleeding that required blood transfusions, and failure to thrive. Laboratory testing at age 2.5 years showed elevated liver transaminases and alkaline phosphatase. Liver biopsy demonstrated portal and periportal fibrosis and hepatocytes with foci of hepatocytic cholestasis. Analysis of bile acids in a blood spot were normal. Treatment with ursodiol and cholestyramine was started at 5 years of age. The coagulopathy resolved and his growth was adequate, but his liver transaminases, direct bilirubin, and GGT levels remained elevated.
Sources: Literature
Mendeliome v0.8822 SUPT16H Zornitza Stark Phenotypes for gene: SUPT16H were changed from Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, MIM# 619480; Intellectual disability; Abnormality of the corpus callosum
Mendeliome v0.8821 SUPT16H Zornitza Stark edited their review of gene: SUPT16H: Changed phenotypes: Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, MIM# 619480, Intellectual disability, Abnormality of the corpus callosum
Mendeliome v0.8821 MOCOS Zornitza Stark Marked gene: MOCOS as ready
Mendeliome v0.8821 MOCOS Zornitza Stark Gene: mocos has been classified as Green List (High Evidence).
Mendeliome v0.8821 MOCOS Zornitza Stark Phenotypes for gene: MOCOS were changed from to Xanthinuria type II, MIM#603592
Mendeliome v0.8820 MOCOS Zornitza Stark Publications for gene: MOCOS were set to
Mendeliome v0.8819 MOCOS Zornitza Stark Mode of inheritance for gene: MOCOS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8818 MOCOS Zornitza Stark reviewed gene: MOCOS: Rating: GREEN; Mode of pathogenicity: None; Publications: 11302742, 17368066, 14624414, 25967871, 34356852, 32073534, 30758870, 27919260; Phenotypes: Xanthinuria type II, MIM#603592; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8818 HNMT Zornitza Stark Marked gene: HNMT as ready
Mendeliome v0.8818 HNMT Zornitza Stark Gene: hnmt has been classified as Green List (High Evidence).
Mendeliome v0.8818 HNMT Zornitza Stark Phenotypes for gene: HNMT were changed from to Mental retardation, autosomal recessive 51, MIM#616739
Mendeliome v0.8817 HNMT Zornitza Stark Publications for gene: HNMT were set to
Mendeliome v0.8816 HNMT Zornitza Stark Mode of inheritance for gene: HNMT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8815 HNMT Zornitza Stark reviewed gene: HNMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 26206890, 30744146, 33310825, 33739554; Phenotypes: Mental retardation, autosomal recessive 51, MIM#616739; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8815 BLNK Zornitza Stark Marked gene: BLNK as ready
Mendeliome v0.8815 BLNK Zornitza Stark Gene: blnk has been classified as Green List (High Evidence).
Mendeliome v0.8815 BLNK Zornitza Stark Phenotypes for gene: BLNK were changed from to Agammaglobulinaemia 4, MIM# 613502
Mendeliome v0.8814 BLNK Zornitza Stark Publications for gene: BLNK were set to
Mendeliome v0.8813 BLNK Zornitza Stark Mode of inheritance for gene: BLNK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8812 BLNK Zornitza Stark reviewed gene: BLNK: Rating: GREEN; Mode of pathogenicity: None; Publications: 10583958, 32194234, 25893637; Phenotypes: Agammaglobulinaemia 4, MIM# 613502; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8812 AICDA Zornitza Stark Marked gene: AICDA as ready
Mendeliome v0.8812 AICDA Zornitza Stark Gene: aicda has been classified as Green List (High Evidence).
Mendeliome v0.8812 AICDA Zornitza Stark Phenotypes for gene: AICDA were changed from to Immunodeficiency with hyper-IgM, type 2, MIM# 605258
Mendeliome v0.8811 AICDA Zornitza Stark Publications for gene: AICDA were set to
Mendeliome v0.8810 AICDA Zornitza Stark Mode of inheritance for gene: AICDA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8809 AICDA Zornitza Stark reviewed gene: AICDA: Rating: GREEN; Mode of pathogenicity: None; Publications: 11007475; Phenotypes: Immunodeficiency with hyper-IgM, type 2, MIM# 605258; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8809 SLC51B Zornitza Stark Phenotypes for gene: SLC51B were changed from Congenital diarrhoea; Cholestasis to Bile acid malabsorption, primary, 2, MIM# 619481; Congenital diarrhoea; Cholestasis
Mendeliome v0.8808 SLC51B Zornitza Stark edited their review of gene: SLC51B: Changed phenotypes: Bile acid malabsorption, primary, 2, MIM# 619481, Congenital diarrhoea, Cholestasis
Mendeliome v0.8808 VPS50 Zornitza Stark Marked gene: VPS50 as ready
Mendeliome v0.8808 VPS50 Zornitza Stark Gene: vps50 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8808 VPS50 Zornitza Stark Classified gene: VPS50 as Amber List (moderate evidence)
Mendeliome v0.8808 VPS50 Zornitza Stark Gene: vps50 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8807 VPS50 Zornitza Stark gene: VPS50 was added
gene: VPS50 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: VPS50 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS50 were set to 34037727
Phenotypes for gene: VPS50 were set to Neonatal cholestatic liver disease; Failure to thrive; Profound global developmental delay; Postnatal microcephaly; Seizures; Abnormality of the corpus callosum
Review for gene: VPS50 was set to AMBER
Added comment: Schneeberger et al (2021 - PMID: 34037727) describe the phenotype of 2 unrelated individuals with biallelic VPS50 variants.

Common features included transient neonatal cholestasis, failure to thrive, severe DD with failure to achieve milestones (last examination at 2y and 2y2m respectively), postnatal microcephaly, seizures (onset at 6m and 25m) and irritability. There was corpus callosum hypoplasia on brain imaging.

Both individuals were homozygous for variants private to each family (no/not known consanguinity applying to each case). The first individual was homozygous for a splicing variant (NM_017667.4:c.1978-1G>T) and had a similarly unaffected sister deceased with no available DNA for testing. The other individual was homozygous for an in-frame deletion (c.1823_1825delCAA / p.(Thr608del)).

VPS50 encodes a critical component of the endosome-associated recycling protein (EARP) complex, which functions in recycling endocytic vesicles back to the plasma membrane [OMIM based on Schindler et al]. The complex contains VPS50, VPS51, VPS52, VPS53, the three latter also being components of GARP (Golgi-associated-retrograde protein) complex. GARP contains VPS54 instead of VPS50 and is required for trafficking of proteins to the trans-golgi network. Thus VPS50 (also named syndetin) and VPS54 function in the EARP and GARP complexes, to define directional movement of their endocytic vesicles [OMIM based on Schindler et al]. The VPS50 subunit is required for recycling of the transferrin receptor.

As discussed by Schneeberger et al (refs provided in text):
- VPS50 has a high expression in mouse and human brain as well as throughout mouse brain development.
- Mice deficient for Vps50 have not been reported. vps50 knockdown in zebrafish results in severe developmental defects of the body axis. Knockout mice for other proteins of the EARP/GARP complex (e.g. Vps52, 53 and 54) display embryonic lethality.

Studies performed by Schneeberger et al included:
- Transcript analysis for the 1st variant demonstrated skipping of ex21 (in patient derived fabriblasts) leading to an in frame deletion of 81 bp (r.1978_2058del) with predicted loss of 27 residues (p.Leu660_Leu686del).
- Similar VPS50 mRNA levels but significant reduction of protein levels (~5% and ~8% of controls) were observed in fibroblasts from patients 1 and 2. Additionally, significant reductions in the amounts of VPS52 and VPS53 protein levels were observed despite mRNA levels similar to controls. Overall, this suggested drastic reduction of functional EARP complex levels.
- Lysosomes appeared to have similar morphology, cellular distribution and likely unaffected function in patient fibroblasts.
- Transferrin receptor recycling was shown to be delayed in patient fibroblasts suggestive of compromise of endocytic-recycling function.

As the authors comment, the phenotype of both individuals with biallelic VPS50 variants overlaps with the corresponding phenotype reported in 15 subjects with biallelic VPS53 or VPS51 mutations notably, severe DD/ID, microcephaly and early onset epilepsy, CC anomalies. Overall, for this group, they propose the term "GARP and/or EARP deficiency disorders".

There is no VPS50-associated phenotype in OMIM or G2P. SysID includes VPS50 among the ID candidate genes.
Sources: Literature
Mendeliome v0.8806 SP6 Zornitza Stark Publications for gene: SP6 were set to 32167558; 18156176; 18297738; 22676574
Mendeliome v0.8805 SP6 Zornitza Stark Mode of inheritance for gene: SP6 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8804 SP6 Zornitza Stark Classified gene: SP6 as Green List (high evidence)
Mendeliome v0.8804 SP6 Zornitza Stark Gene: sp6 has been classified as Green List (High Evidence).
Mendeliome v0.8803 SP6 Zornitza Stark reviewed gene: SP6: Rating: GREEN; Mode of pathogenicity: None; Publications: 33652941; Phenotypes: Hypoplastic amelogenesis imperfecta; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8803 AMTN Zornitza Stark Marked gene: AMTN as ready
Mendeliome v0.8803 AMTN Zornitza Stark Gene: amtn has been classified as Red List (Low Evidence).
Mendeliome v0.8803 AMTN Zornitza Stark gene: AMTN was added
gene: AMTN was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: AMTN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AMTN were set to 27412008; 25715379; 26620968
Phenotypes for gene: AMTN were set to Amelogenesis imperfecta, type IIIB
Mode of pathogenicity for gene: AMTN was set to Other
Review for gene: AMTN was set to RED
Added comment: In a Costa Rican family segregating autosomal dominant hypomineralized amelogenesis imperfecta, Smith et al. (2016) identified a heterozygous deletion/insertion mutation in the amelotin gene that segregated with the phenotype in the family. The mutation was predicted to result in an in-frame deletion of 92 amino acids, shortening the protein from 209 to 117 amino acids. Mode of pathogenicity not established. Toxic gain of function proposed as Atmn KO and +/- mice did not recapitulate the human phenotype.
Sources: Expert Review
Mendeliome v0.8802 WDR72 Zornitza Stark Marked gene: WDR72 as ready
Mendeliome v0.8802 WDR72 Zornitza Stark Gene: wdr72 has been classified as Green List (High Evidence).
Mendeliome v0.8802 WDR72 Zornitza Stark Phenotypes for gene: WDR72 were changed from to Amelogenesis imperfecta, type IIA3, MIM# 613211
Mendeliome v0.8801 WDR72 Zornitza Stark Publications for gene: WDR72 were set to
Mendeliome v0.8800 WDR72 Zornitza Stark Mode of inheritance for gene: WDR72 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8799 WDR72 Zornitza Stark reviewed gene: WDR72: Rating: GREEN; Mode of pathogenicity: None; Publications: 21196691, 27259663, 20938048, 26502894, 23293580, 25008349, 19853237; Phenotypes: Amelogenesis imperfecta, type IIA3, MIM# 613211; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8799 SLC24A4 Zornitza Stark Marked gene: SLC24A4 as ready
Mendeliome v0.8799 SLC24A4 Zornitza Stark Gene: slc24a4 has been classified as Green List (High Evidence).
Mendeliome v0.8799 SLC24A4 Zornitza Stark Phenotypes for gene: SLC24A4 were changed from to Amelogenesis imperfecta, type IIA5, MIM# 615887
Mendeliome v0.8798 SLC24A4 Zornitza Stark Publications for gene: SLC24A4 were set to
Mendeliome v0.8797 SLC24A4 Zornitza Stark Mode of inheritance for gene: SLC24A4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8796 SLC24A4 Zornitza Stark reviewed gene: SLC24A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 23375655, 24621671, 25442250, 24532815, 26502894, 27129268; Phenotypes: Amelogenesis imperfecta, type IIA5, MIM# 615887; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8796 ROGDI Zornitza Stark Marked gene: ROGDI as ready
Mendeliome v0.8796 ROGDI Zornitza Stark Gene: rogdi has been classified as Green List (High Evidence).
Mendeliome v0.8796 ROGDI Zornitza Stark Phenotypes for gene: ROGDI were changed from to Kohlschutter-Tonz syndrome, MIM# 226750
Mendeliome v0.8795 ROGDI Zornitza Stark Publications for gene: ROGDI were set to
Mendeliome v0.8794 ROGDI Zornitza Stark Mode of inheritance for gene: ROGDI was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8793 ROGDI Zornitza Stark reviewed gene: ROGDI: Rating: GREEN; Mode of pathogenicity: None; Publications: 22424600, 23086778, 33866847; Phenotypes: Kohlschutter-Tonz syndrome, MIM# 226750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8793 RELT Zornitza Stark Marked gene: RELT as ready
Mendeliome v0.8793 RELT Zornitza Stark Gene: relt has been classified as Green List (High Evidence).
Mendeliome v0.8793 RELT Zornitza Stark Classified gene: RELT as Green List (high evidence)
Mendeliome v0.8793 RELT Zornitza Stark Gene: relt has been classified as Green List (High Evidence).
Mendeliome v0.8792 RELT Zornitza Stark gene: RELT was added
gene: RELT was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: RELT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RELT were set to 30506946
Phenotypes for gene: RELT were set to Amelogenesis imperfecta, type IIIC, MIM# 618386
Review for gene: RELT was set to GREEN
Added comment: Amelogenesis imperfecta type IIIC is characterized by hypocalcified enamel in both the primary and secondary dentition. The enamel is rough and yellow-brown; under normal use, the enamel disintegrates from occlusal surfaces of the molars, leaving a ring of intact enamel remaining on the sides. At least 3 families and a mouse model.
Sources: Expert Review
Mendeliome v0.8791 LAMB3 Zornitza Stark Phenotypes for gene: LAMB3 were changed from Epidermolysis bullosa, junctional, Herlitz type, MIM# 226700; Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650 to Amelogenesis imperfecta, type IA, MIM# 104530; Epidermolysis bullosa, junctional, Herlitz type, MIM# 226700; Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650
Mendeliome v0.8790 LAMB3 Zornitza Stark Publications for gene: LAMB3 were set to 11023379; 7706760
Mendeliome v0.8789 LAMB3 Zornitza Stark Mode of inheritance for gene: LAMB3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.8788 LAMB3 Zornitza Stark edited their review of gene: LAMB3: Changed publications: 11023379, 7706760, 23958762, 7706760, 23632796, 26502894, 27220909, 25769099, 24494736; Changed phenotypes: Amelogenesis imperfecta, type IA, MIM# 104530, Epidermolysis bullosa, junctional, Herlitz type, MIM# 226700, Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.8788 KIAA0753 Zornitza Stark Phenotypes for gene: KIAA0753 were changed from Orofaciodigital syndrome XV, MIM# 617127; Joubert syndrome 38, MIM# 619476 to Orofaciodigital syndrome XV, MIM# 617127; Joubert syndrome 38, MIM# 619476; Short-rib thoracic dysplasia 21 without polydactyly, MIM# 619479
Mendeliome v0.8787 KIAA0753 Zornitza Stark Publications for gene: KIAA0753 were set to 31816441; 28220259; 29138412; 26643951
Mendeliome v0.8786 KIAA0753 Zornitza Stark edited their review of gene: KIAA0753: Added comment: At least 5 families reported with a skeletal ciliopathy.; Changed publications: 29138412, 31816441, 33875766, 34016807; Changed phenotypes: Orofaciodigital syndrome XV 617127, Joubert syndrome, Short-rib thoracic dysplasia 21 without polydactyly, MIM# 619479
Mendeliome v0.8786 SPTBN1 Zornitza Stark Phenotypes for gene: SPTBN1 were changed from Neurodevelopmental Syndrome; Intellectual disability; Seizures to Developmental delay, impaired speech, and behavioural abnormalities, MIM# 619475; Neurodevelopmental Syndrome; Intellectual disability; Seizures
Mendeliome v0.8785 SPTBN1 Zornitza Stark reviewed gene: SPTBN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental delay, impaired speech, and behavioural abnormalities, MIM# 619475; Mode of inheritance: None
Mendeliome v0.8785 NIID Zornitza Stark Phenotypes for STR: NIID were changed from Neuronal intranuclear inclusion disease MIM#603472; Tremor, hereditary essential, 6 MIM#618866 to Neuronal intranuclear inclusion disease MIM#603472; Tremor, hereditary essential, 6 MIM#618866; Oculopharyngodistal myopathy 3, MIM# 619473
Mendeliome v0.8784 NIID Zornitza Stark reviewed STR: NIID: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Oculopharyngodistal myopathy 3, MIM# 619473; Mode of inheritance: None
Mendeliome v0.8784 KLK4 Zornitza Stark Marked gene: KLK4 as ready
Mendeliome v0.8784 KLK4 Zornitza Stark Gene: klk4 has been classified as Green List (High Evidence).
Mendeliome v0.8784 KLK4 Zornitza Stark Phenotypes for gene: KLK4 were changed from to Amelogenesis imperfecta, type IIA1, MIM# 204700
Mendeliome v0.8783 KLK4 Zornitza Stark Publications for gene: KLK4 were set to
Mendeliome v0.8782 KLK4 Zornitza Stark Mode of inheritance for gene: KLK4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8781 KLK4 Zornitza Stark reviewed gene: KLK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 15235027, 23355523, 28611678, 27066511; Phenotypes: Amelogenesis imperfecta, type IIA1, MIM# 204700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8781 ITGB6 Zornitza Stark Marked gene: ITGB6 as ready
Mendeliome v0.8781 ITGB6 Zornitza Stark Gene: itgb6 has been classified as Green List (High Evidence).
Mendeliome v0.8781 ITGB6 Zornitza Stark Classified gene: ITGB6 as Green List (high evidence)
Mendeliome v0.8781 ITGB6 Zornitza Stark Gene: itgb6 has been classified as Green List (High Evidence).
Mendeliome v0.8780 ITGB6 Zornitza Stark gene: ITGB6 was added
gene: ITGB6 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ITGB6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITGB6 were set to 25431241; 26695873; 24305999; 24319098
Phenotypes for gene: ITGB6 were set to Amelogenesis imperfecta, type IH, MIM# 616221
Review for gene: ITGB6 was set to GREEN
Added comment: At least 3 unrelated families reported.
Sources: Expert Review
Mendeliome v0.8779 STAT3 Zornitza Stark Marked gene: STAT3 as ready
Mendeliome v0.8779 STAT3 Zornitza Stark Gene: stat3 has been classified as Green List (High Evidence).
Mendeliome v0.8779 STAT3 Zornitza Stark Phenotypes for gene: STAT3 were changed from to Hyper-IgE recurrent infection syndrome MIM# 147060; Autoimmune disease, multisystem, infantile-onset, 1 MIM# 615952
Mendeliome v0.8778 STAT3 Zornitza Stark Publications for gene: STAT3 were set to
Mendeliome v0.8777 STAT3 Zornitza Stark Mode of inheritance for gene: STAT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8776 STAT3 Zornitza Stark reviewed gene: STAT3: Rating: GREEN; Mode of pathogenicity: None; Publications: 17881745, 14566054, 25349174, 25038750, 25359994; Phenotypes: Hyper-IgE recurrent infection syndrome MIM# 147060, Autoimmune disease, multisystem, infantile-onset, 1 MIM# 615952; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8776 STK4 Zornitza Stark Marked gene: STK4 as ready
Mendeliome v0.8776 STK4 Zornitza Stark Gene: stk4 has been classified as Green List (High Evidence).
Mendeliome v0.8776 STK4 Zornitza Stark Phenotypes for gene: STK4 were changed from to T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations MIM# 614868; CD4/CD8 lymphopaenia; cardiac malformations; reduced naïve T cells; increased TEM and TEMRA cells; poor T cell Proliferation; Reduced memory B cells; Reduced IgM, increased IgG, IgA, IgE; impaired antibody responses; intermittent neutropaenia; bacterial/ viral/ fungal infections; autoimmune cytopaenias; mucocutaneous candidiasis; cutaneous warts
Mendeliome v0.8775 STK4 Zornitza Stark Publications for gene: STK4 were set to
Mendeliome v0.8774 STK4 Zornitza Stark Mode of inheritance for gene: STK4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8773 SP110 Zornitza Stark Marked gene: SP110 as ready
Mendeliome v0.8773 SP110 Zornitza Stark Gene: sp110 has been classified as Green List (High Evidence).
Mendeliome v0.8773 SP110 Zornitza Stark Tag founder tag was added to gene: SP110.
Mendeliome v0.8773 SP110 Zornitza Stark Phenotypes for gene: SP110 were changed from to Hepatic veno-occlusive disease with immunodeficiency MIM#235550; Hepatic veno-occlusive disease; susceptibility to Pneumocystis jirovecii pneumonia; cytomegalovirus; thrombocytopaenia; hepatosplenomegaly; cerebrospinal leukodystrophy; memory T/B cell deficiency; low Ig levels; absent tissue plasma cells; absent lymph node germinal centers; hypogammaglobulinaemia
Mendeliome v0.8772 SP110 Zornitza Stark Publications for gene: SP110 were set to
Mendeliome v0.8771 SP110 Zornitza Stark Mode of inheritance for gene: SP110 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8770 SMARCAL1 Zornitza Stark Marked gene: SMARCAL1 as ready
Mendeliome v0.8770 SMARCAL1 Zornitza Stark Gene: smarcal1 has been classified as Green List (High Evidence).
Mendeliome v0.8770 SMARCAL1 Zornitza Stark Phenotypes for gene: SMARCAL1 were changed from to Schimke immune-osseous dysplasia MIM# 242900; T cell deficiency; Short stature; spondyloepiphyseal dysplasia; renal dysfunction; lymphocytopaenia; nephropathy; bacterial/viral/fungal infections; may present as SCID; bone marrow failure
Mendeliome v0.8769 SMARCAL1 Zornitza Stark Publications for gene: SMARCAL1 were set to
Mendeliome v0.8768 SMARCAL1 Zornitza Stark Mode of inheritance for gene: SMARCAL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8767 STK4 Danielle Ariti reviewed gene: STK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22294732, 26117625, 22174160, 22952854; Phenotypes: T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations MIM# 614868, CD4/CD8 lymphopaenia, cardiac malformations, reduced naïve T cells, increased TEM and TEMRA cells, poor T cell Proliferation, Reduced memory B cells, Reduced IgM, increased IgG, IgA, IgE, impaired antibody responses, intermittent neutropaenia, bacterial/ viral/ fungal infections, autoimmune cytopaenias, mucocutaneous candidiasis, cutaneous warts; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8767 SPINK5 Danielle Ariti reviewed gene: SPINK5: Rating: ; Mode of pathogenicity: None; Publications: 33534181, 20657595; Phenotypes: Netherton syndrome MIM# 256500, Low switched and non-switched B cells, High IgE and IgA, Antibody variably decreased, Congenital ichthyosis, bamboo hair, atopic diathesis, increased bacterial infections, failure to thrive, food allergies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8767 SP110 Danielle Ariti reviewed gene: SP110: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301448, 31721003; Phenotypes: Hepatic veno-occlusive disease with immunodeficiency MIM#235550, Hepatic veno-occlusive disease, susceptibility to Pneumocystis jirovecii pneumonia, cytomegalovirus, thrombocytopaenia, hepatosplenomegaly, cerebrospinal leukodystrophy, memory T/B cell deficiency, low Ig levels, absent tissue plasma cells, absent lymph node germinal centers, hypogammaglobulinaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8767 SMARCAL1 Danielle Ariti reviewed gene: SMARCAL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301550, 17089404, 20036229; Phenotypes: Schimke immune-osseous dysplasia MIM# 242900, T cell deficiency, Short stature, spondyloepiphyseal dysplasia, renal dysfunction, lymphocytopaenia, nephropathy, bacterial/viral/fungal infections, may present as SCID, bone marrow failure; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8767 GPR68 Zornitza Stark Marked gene: GPR68 as ready
Mendeliome v0.8767 GPR68 Zornitza Stark Gene: gpr68 has been classified as Green List (High Evidence).
Mendeliome v0.8767 GPR68 Zornitza Stark Phenotypes for gene: GPR68 were changed from to Amelogenesis imperfecta, hypomaturation type, IIA6 MIM#617217
Mendeliome v0.8766 GPR68 Zornitza Stark Publications for gene: GPR68 were set to
Mendeliome v0.8765 GPR68 Zornitza Stark Mode of inheritance for gene: GPR68 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8764 GPR68 Zornitza Stark reviewed gene: GPR68: Rating: GREEN; Mode of pathogenicity: None; Publications: 27693231, 32279993; Phenotypes: Amelogenesis imperfecta, hypomaturation type, IIA6 MIM#617217; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8764 FAM83H Zornitza Stark Marked gene: FAM83H as ready
Mendeliome v0.8764 FAM83H Zornitza Stark Gene: fam83h has been classified as Green List (High Evidence).
Mendeliome v0.8764 FAM83H Zornitza Stark Phenotypes for gene: FAM83H were changed from to Amelogenesis imperfecta, type IIIA MIM#130900
Mendeliome v0.8763 FAM83H Zornitza Stark Publications for gene: FAM83H were set to
Mendeliome v0.8762 FAM83H Zornitza Stark Mode of inheritance for gene: FAM83H was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8761 FAM83H Zornitza Stark reviewed gene: FAM83H: Rating: GREEN; Mode of pathogenicity: None; Publications: 18484629, 19407157, 19825039, 26481691, 21702852, 20160442, 26142250, 22414746, 19828885, 19220331, 26502894, 18252228, 21597265, 21118793, 26788537, 26171361; Phenotypes: Amelogenesis imperfecta, type IIIA MIM#130900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8761 ENAM Zornitza Stark Marked gene: ENAM as ready
Mendeliome v0.8761 ENAM Zornitza Stark Gene: enam has been classified as Green List (High Evidence).
Mendeliome v0.8761 ENAM Zornitza Stark Phenotypes for gene: ENAM were changed from to Amelogenesis imperfecta, type IB, MIM# 104500; Amelogenesis imperfecta, type IC, MIM# 204650
Mendeliome v0.8760 ENAM Zornitza Stark Publications for gene: ENAM were set to
Mendeliome v0.8759 ENAM Zornitza Stark Mode of inheritance for gene: ENAM was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8758 ENAM Zornitza Stark reviewed gene: ENAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 11487571, 28334996, 14684688, 33864320; Phenotypes: Amelogenesis imperfecta, type IB, MIM# 104500, Amelogenesis imperfecta, type IC, MIM# 204650; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8758 FAM20A Zornitza Stark Marked gene: FAM20A as ready
Mendeliome v0.8758 FAM20A Zornitza Stark Gene: fam20a has been classified as Green List (High Evidence).
Mendeliome v0.8758 FAM20A Zornitza Stark Phenotypes for gene: FAM20A were changed from to Amelogenesis imperfecta, type IG (enamel-renal syndrome) MIM#204690
Mendeliome v0.8757 FAM20A Zornitza Stark Publications for gene: FAM20A were set to
Mendeliome v0.8756 FAM20A Zornitza Stark Mode of inheritance for gene: FAM20A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8755 FAM20A Zornitza Stark reviewed gene: FAM20A: Rating: GREEN; Mode of pathogenicity: None; Publications: 23434854, 23697977, 23468644, 24756937, 21549343, 24259279, 24196488, 26502894, 25827751, 21990045; Phenotypes: Amelogenesis imperfecta, type IG (enamel-renal syndrome) MIM#204690; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8755 C4orf26 Zornitza Stark Marked gene: C4orf26 as ready
Mendeliome v0.8755 C4orf26 Zornitza Stark Gene: c4orf26 has been classified as Green List (High Evidence).
Mendeliome v0.8755 C4orf26 Zornitza Stark Phenotypes for gene: C4orf26 were changed from to Amelogenesis imperfecta, type IIA4, MIM# 614832
Mendeliome v0.8754 C4orf26 Zornitza Stark Publications for gene: C4orf26 were set to
Mendeliome v0.8753 C4orf26 Zornitza Stark Mode of inheritance for gene: C4orf26 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8752 C4orf26 Zornitza Stark reviewed gene: C4orf26: Rating: GREEN; Mode of pathogenicity: None; Publications: 22901946, 27558265; Phenotypes: Amelogenesis imperfecta, type IIA4, MIM# 614832; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8752 AMELX Zornitza Stark Marked gene: AMELX as ready
Mendeliome v0.8752 AMELX Zornitza Stark Gene: amelx has been classified as Green List (High Evidence).
Mendeliome v0.8752 AMELX Zornitza Stark Phenotypes for gene: AMELX were changed from Amelogenesis imperfecta, type 1E, MIM# 301200 to Amelogenesis imperfecta, type 1E, MIM# 301200
Mendeliome v0.8752 AMELX Zornitza Stark Phenotypes for gene: AMELX were changed from to Amelogenesis imperfecta, type 1E, MIM# 301200
Mendeliome v0.8751 AMELX Zornitza Stark Publications for gene: AMELX were set to
Mendeliome v0.8750 AMELX Zornitza Stark Mode of inheritance for gene: AMELX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.8749 AMELX Zornitza Stark Tag SV/CNV tag was added to gene: AMELX.
Mendeliome v0.8749 AMELX Zornitza Stark reviewed gene: AMELX: Rating: GREEN; Mode of pathogenicity: None; Publications: 17189466, 22243263, 7599636, 23251683, 1483698 1916828, 9188994, 15111628, 11201048, 26502894, 7782077, 11922869, 28130977, 8406474, 11839357, 25117480, 19610109; Phenotypes: Amelogenesis imperfecta, type 1E, MIM# 301200; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.8749 AMBN Zornitza Stark Marked gene: AMBN as ready
Mendeliome v0.8749 AMBN Zornitza Stark Gene: ambn has been classified as Green List (High Evidence).
Mendeliome v0.8749 AMBN Zornitza Stark Phenotypes for gene: AMBN were changed from to Amelogenesis imperfecta, type IF MIM#616270
Mendeliome v0.8748 AMBN Zornitza Stark Publications for gene: AMBN were set to
Mendeliome v0.8747 AMBN Zornitza Stark Mode of inheritance for gene: AMBN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8746 AMBN Zornitza Stark reviewed gene: AMBN: Rating: GREEN; Mode of pathogenicity: None; Publications: 24858907, 26502894, 31402633, 30174330; Phenotypes: Amelogenesis imperfecta, type IF MIM#616270; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8746 ACP4 Zornitza Stark reviewed gene: ACP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28513613, 27843125, 33552707; Phenotypes: Amelogenesis imperfecta, type IJ MIM#617297; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8746 KIAA0753 Zornitza Stark Phenotypes for gene: KIAA0753 were changed from Orofaciodigital syndrome XV, MIM# 617127; Joubert syndrome to Orofaciodigital syndrome XV, MIM# 617127; Joubert syndrome 38, MIM# 619476
Mendeliome v0.8745 TMEM222 Zornitza Stark Phenotypes for gene: TMEM222 were changed from Intellectual disability; Epilepsy; Microcephaly to Neurodevelopmental disorder with motor and speech delay and behavioural abnormalities, MIM# 619470; Intellectual disability; Epilepsy; Microcephaly
Mendeliome v0.8744 TMEM222 Zornitza Stark edited their review of gene: TMEM222: Changed phenotypes: Neurodevelopmental disorder with motor and speech delay and behavioural abnormalities, MIM# 619470, Intellectual disability, Epilepsy, Microcephaly
Mendeliome v0.8744 TCF7L2 Zornitza Stark Phenotypes for gene: TCF7L2 were changed from Developmental disorders to Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Myopia; Abnormality of skeletal system
Mendeliome v0.8743 TCF7L2 Zornitza Stark Publications for gene: TCF7L2 were set to 33057194
Mendeliome v0.8742 TCF7L2 Zornitza Stark Classified gene: TCF7L2 as Green List (high evidence)
Mendeliome v0.8742 TCF7L2 Zornitza Stark Gene: tcf7l2 has been classified as Green List (High Evidence).
Mendeliome v0.8741 TCF7L2 Zornitza Stark changed review comment from: 2 reviews
Konstantinos Varvagiannis (Other)
I don't know

Dias et al (2021 - PMID: 34003604) describe the phenotype of 11 unrelated individuals harboring de novo missense/truncating TCF7L2 variants.

Features included DD in childhood (motor delay in 8/11, speech delay in 11/11), intellectual abilities ranging from average cognitive functioning to mild/moderate ID (the latter observed in 5/11), myopia (6/11) , dysmorphic features, variable orthopedic findings, and neuropsychiatric comorbidities incl. ASD (4/11) / ADHD (4/11).

One additional (12th) individual was excluded from this summary due to concurrent diagnosis of hypoxic-ischemic injury.

TCF7L2 on 10q25 encodes transcription factor 7-like 2, a high mobility group (HMG) box-containing transcription factor. As the authors discuss, the protein mediates canonical Wnt signaling. Secreted Wnt proteins lead to release of beta-catenin (CTNNB1) which after translocation to the nucleus acts with DNA-binding factors incl. TCF7L2 to turn on Wnt-responsive target genes. As a result TCF7L2 acts with beta-catenin as a switch for transcriptional regulation. Multiple alternative spliced TCF7L2 transcripts mediate it's function and specificity of transcriptional repertoire in a variety of tissues and contexts.

Dias et al provide references for its role in nervous system development incl. neurogenesis and thalamic development.

Variants in all cases occurred as de novo events with pLoF (stopgain, frameshift, splicing) ones predicted to lead to NMD. Missense variants occurred in all cases in or adjacent to the HMG box domain [aa 350-417]. 5 different missense variants affecting 3 residues were reported incl. c.1142A>C, c.1143C>G (leading to Asn381Thr/Lys respectively), c.1250G>T (Trp417Leu), c.1267T>C, c.1268A>G (leading to Tyr423His/Cys) [NM_001146274.1].

The gene has a pLI of 0.99-1 gnomAD/ExAC while there is a region of missense constraint encompassing the HMG box domain (the latter is an evolutionary conserved region mediating interactions with DNA).

No phenotypic differences were observed among individuals with pLoF and missense SNVs, and haploinsufficiency is presumed to be the underlying mechanism.

There are no variant or other studies performed, nor any animal models discussed.

In supplementary table 2, the authors provide several references to previous large scale sequencing studies with brief/incomplete descriptions of individuals de novo TCF7L2 variants and neurodevelopmental disorder (ID/ASD - Iossifov, De Rubeis, Lelieveld, McRae/DDD study and many other Refs).

Heterozygous TCF7L2 variants are thought to confer susceptibility to type diabetes mellitus (MIM 125853). Individuals reported by Dias et al did not have endocrine abnormalities including DM. A study by Roychowdhury et al (2021 - PMID: 34265237) suggests that regulatory variants in TCF7L2 are associated with thoracic aneurysm.

There is no other associated phenotype (notably NDD) in OMIM.
G2P includes TCF7L2 in its DD panel (Disease : TC7L2-related DD, Confidence:confirmed, Monoallelic, LoF).
SysID includes this gene within the autism candidate genes and current primary ID genes.; to: Dias et al (2021 - PMID: 34003604) describe the phenotype of 11 unrelated individuals harboring de novo missense/truncating TCF7L2 variants.

Features included DD in childhood (motor delay in 8/11, speech delay in 11/11), intellectual abilities ranging from average cognitive functioning to mild/moderate ID (the latter observed in 5/11), myopia (6/11) , dysmorphic features, variable orthopedic findings, and neuropsychiatric comorbidities incl. ASD (4/11) / ADHD (4/11).

One additional (12th) individual was excluded from this summary due to concurrent diagnosis of hypoxic-ischemic injury.

TCF7L2 on 10q25 encodes transcription factor 7-like 2, a high mobility group (HMG) box-containing transcription factor. As the authors discuss, the protein mediates canonical Wnt signaling. Secreted Wnt proteins lead to release of beta-catenin (CTNNB1) which after translocation to the nucleus acts with DNA-binding factors incl. TCF7L2 to turn on Wnt-responsive target genes. As a result TCF7L2 acts with beta-catenin as a switch for transcriptional regulation. Multiple alternative spliced TCF7L2 transcripts mediate it's function and specificity of transcriptional repertoire in a variety of tissues and contexts.

Dias et al provide references for its role in nervous system development incl. neurogenesis and thalamic development.

Variants in all cases occurred as de novo events with pLoF (stopgain, frameshift, splicing) ones predicted to lead to NMD. Missense variants occurred in all cases in or adjacent to the HMG box domain [aa 350-417]. 5 different missense variants affecting 3 residues were reported incl. c.1142A>C, c.1143C>G (leading to Asn381Thr/Lys respectively), c.1250G>T (Trp417Leu), c.1267T>C, c.1268A>G (leading to Tyr423His/Cys) [NM_001146274.1].

The gene has a pLI of 0.99-1 gnomAD/ExAC while there is a region of missense constraint encompassing the HMG box domain (the latter is an evolutionary conserved region mediating interactions with DNA).

No phenotypic differences were observed among individuals with pLoF and missense SNVs, and haploinsufficiency is presumed to be the underlying mechanism.

There are no variant or other studies performed, nor any animal models discussed.

In supplementary table 2, the authors provide several references to previous large scale sequencing studies with brief/incomplete descriptions of individuals de novo TCF7L2 variants and neurodevelopmental disorder (ID/ASD - Iossifov, De Rubeis, Lelieveld, McRae/DDD study and many other Refs).

Heterozygous TCF7L2 variants are thought to confer susceptibility to type diabetes mellitus (MIM 125853). Individuals reported by Dias et al did not have endocrine abnormalities including DM. A study by Roychowdhury et al (2021 - PMID: 34265237) suggests that regulatory variants in TCF7L2 are associated with thoracic aneurysm.

There is no other associated phenotype (notably NDD) in OMIM.
G2P includes TCF7L2 in its DD panel (Disease : TC7L2-related DD, Confidence:confirmed, Monoallelic, LoF).
SysID includes this gene within the autism candidate genes and current primary ID genes.
Mendeliome v0.8741 TCF7L2 Zornitza Stark reviewed gene: TCF7L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34003604; Phenotypes: Global developmental delay, Intellectual disability, Autism, Attention deficit hyperactivity disorder, Myopia, Abnormality of skeletal system; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8741 LTBP3 Zornitza Stark Marked gene: LTBP3 as ready
Mendeliome v0.8741 LTBP3 Zornitza Stark Gene: ltbp3 has been classified as Green List (High Evidence).
Mendeliome v0.8741 LTBP3 Zornitza Stark Phenotypes for gene: LTBP3 were changed from to Dental anomalies and short stature, MIM# 601216; Geleophysic dysplasia 3, MIM# 617809; Thoracic aneurysm
Mendeliome v0.8740 LTBP3 Zornitza Stark Publications for gene: LTBP3 were set to
Mendeliome v0.8739 LTBP3 Zornitza Stark Mode of inheritance for gene: LTBP3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8738 LTBP3 Zornitza Stark reviewed gene: LTBP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19344874, 25899461, 25669657, 29625025, 27068007, 34150014; Phenotypes: Dental anomalies and short stature, MIM# 601216, Geleophysic dysplasia 3, MIM# 617809, Thoracic aneurysm; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8738 ARIH1 Zornitza Stark reviewed gene: ARIH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8738 ARIH1 Zornitza Stark Mode of inheritance for gene: ARIH1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8737 PIDD1 Zornitza Stark Marked gene: PIDD1 as ready
Mendeliome v0.8737 PIDD1 Zornitza Stark Gene: pidd1 has been classified as Green List (High Evidence).
Mendeliome v0.8737 PIDD1 Zornitza Stark Classified gene: PIDD1 as Green List (high evidence)
Mendeliome v0.8737 PIDD1 Zornitza Stark Gene: pidd1 has been classified as Green List (High Evidence).
Mendeliome v0.8736 PIDD1 Zornitza Stark gene: PIDD1 was added
gene: PIDD1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: PIDD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIDD1 were set to 28397838; 29302074; 33414379; 34163010
Phenotypes for gene: PIDD1 were set to Global developmental delay; Intellectual disability; Seizures; Autism; Behavioral abnormality; Psychosis; Pachygyria; Lissencephaly; Abnormality of the corpus callosum
Review for gene: PIDD1 was set to GREEN
Added comment: There is enough evidence to include this gene in the current panel with green rating.

Biallelic PIDD1 pathogenic variants have been reported in 26 individuals (11 families) with DD (all), variable degrees of ID (mild to severe), behavioral (eg. aggression/self-mutilation in several, ADHD) and/or psychiatric abnormalities (ASD, psychosis in 5 belonging to 3 families), well-controlled epilepsy is some (9 subjects from 6 families) and MRI abnormalities notably abnormal gyration pattern (pachygyria with predominant anterior gradient) as well as corpus callosum anomalies (commonly thinning) in several. Dysmorphic features have been reported in almost all, although there has been no specific feature suggested.

The first reports on the phenotype associated with biallelic PIDD1 mutations were made by Harripaul et al (2018 - PMID: 28397838) and Hu et al (2019 - PMID: 29302074) [both studies investigating large cohorts of individuals with ID from consanguineous families].

Sheikh et al (2021 - PMID: 33414379) provided details on the phenotype of 15 individuals from 5 families including those from the previous 2 reports and studied provided evidence on the role of PIDD1 and the effect of variants.

Zaki et al (2021 - PMID: 34163010) reported 11 additional individuals from 6 consanguineous families, summarize the features of all subjects published in the literature and review the neuroradiological features of the disorder.

PIDD1 encodes p53-induced death domain protein 1. The protein is part of the PIDDosome, a multiprotein complex also composed of the bipartite linker protein CRADD (also known as RAIDD) and the proform of caspase-2 and induces apoptosis in response to DNA damage.

There are 5 potential PIDD1 mRNA transcript variants with NM_145886.4 corresponding to the longest. Similar to the protein encoded by CRADD, PIDD1 contains a death domain (DD - aa 774-893). Constitutive post-translational processing gives PIDD1-N, PIDD1-C the latter further processed into PIDD1-CC (by auto-cleavage). Serine residues at pos. 446 and 588 are involved in this autoprocessing generating PIDD1-C (aa 446-910) and PIDD1-CC (aa 774-893). The latter is needed for caspase-2 activation.

Most (if not all) individuals belonged to consanguineous families of different origins and harbored pLoF or missense variants.

Variants reported so far include : c.2587C>T; p.Gln863* / c.1909C>T ; p.Arg637* / c.2443C>T / p.Arg815Trp / c.2275-1G>A which upon trap assay was shown to lead to skipping of ex15 with direct splicing form exon14 to the terminal exon 16 (resulting to p.Arg759Glyfs*1 with exlcusion of the entire DD) / c.2584C>T; p.Arg862Trp / c.1340G>A; p.Trp447* / c.2116_2120del; p.Val706His*, c.1564_1565del; p.Gly602fs*26

Evidence so far provided includes:
- Biallelic CRADD variants cause a NDD disorder and a highly similar gyration pattern.
- Confirmation of splicing effect (eg. for c.2275-1G>A premature stop in position 760) or poor expression (NM_145886.3:c.2587C>T; p.Gln863*). Arg815Trp did not affect autoprocessing or protein stability.
- Abnormal localization pattern, loss of interaction with CRADD and failure to activate caspase-2 (MDM2 cleavage assay) [p.Gln863* and Arg815Trp]
- Available expression data from GTEx (PIDD1 having broad expression in multiple tissues, but higher in brain cerebellum) as well as BrainSpan and PsychEncode studies suggesting high coexpression of PIDD1, CRADD and CASP2 in many regions in the developing human brain.
- Variants in other genes encoding proteins interacting with PIDD1 (MADD, FADD, DNAJ, etc) are associated with NDD.

Pidd-1 ko mice (ex3-15 removal) lack however CNS-related phenotypes. These show decreased anxiety but no motor anomalies. This has also been the case with Cradd-/- mice displaying no significant CNS phenotypes without lamination defects.

There is currently no associated phenotype in OMIM. PIDD1 is listed in the DD panel of G2P (PIDD1-related NDD / biallelic / loss of function / probable) . SysID includes PIDD1 among the current primary ID genes.
Sources: Expert Review
Mendeliome v0.8735 COLGALT1 Bryony Thompson Marked gene: COLGALT1 as ready
Mendeliome v0.8735 COLGALT1 Bryony Thompson Gene: colgalt1 has been classified as Green List (High Evidence).
Mendeliome v0.8735 COLGALT1 Bryony Thompson Classified gene: COLGALT1 as Green List (high evidence)
Mendeliome v0.8735 COLGALT1 Bryony Thompson Gene: colgalt1 has been classified as Green List (High Evidence).
Mendeliome v0.8734 COLGALT1 Bryony Thompson gene: COLGALT1 was added
gene: COLGALT1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: COLGALT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COLGALT1 were set to 30412317; 33709034; 31759980
Phenotypes for gene: COLGALT1 were set to Brain small vessel disease 3 MIM#618360
Review for gene: COLGALT1 was set to GREEN
Added comment: 3 unrelated cases with biallelic variants, and supporting functional assays. The main features of the cases were porencephalic cysts, leukoencephalopathy, lacunar infarcts, cerebral microbleeds/haemorrhages and calcifications. A null mouse model was embryonic lethal, but had defects in the vascular networks of the embryos.
Sources: Other
Mendeliome v0.8733 JAKMIP1 Seb Lunke Marked gene: JAKMIP1 as ready
Mendeliome v0.8733 JAKMIP1 Seb Lunke Gene: jakmip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8733 JAKMIP1 Seb Lunke Classified gene: JAKMIP1 as Amber List (moderate evidence)
Mendeliome v0.8733 JAKMIP1 Seb Lunke Gene: jakmip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8732 JAKMIP1 Seb Lunke gene: JAKMIP1 was added
gene: JAKMIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: JAKMIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: JAKMIP1 were set to 29158550; 26627310; 27799067
Phenotypes for gene: JAKMIP1 were set to Intellectual disability; Seizures
Review for gene: JAKMIP1 was set to AMBER
Added comment: Identified in two independent patients in the literature with a mouse model.

Patient 1 (27799067) with developmental delay, speech delay, and cognitive impairment; self-injurious and aggressive behaviour, seizures, dysmorphic features. De-novo missense JAKMIP1 (p.D586H).

Patient 2 (29158550) with feeding difficulties, hypotonia, epilepsy, severe ID, no active speech, kyphoscoliosis, constipation, autism, short stature. Splice variant c.1432-2A>G, no segregation or RNA data available.

KO mouse model (27799067) displays social deficits, stereotyped activity, abnormal postnatal vocalizations, and other autistic-like behaviors.
Sources: Literature
Mendeliome v0.8731 ARIH1 Bryony Thompson Marked gene: ARIH1 as ready
Mendeliome v0.8731 ARIH1 Bryony Thompson Gene: arih1 has been classified as Green List (High Evidence).
Mendeliome v0.8731 ARIH1 Bryony Thompson Classified gene: ARIH1 as Green List (high evidence)
Mendeliome v0.8731 ARIH1 Bryony Thompson Gene: arih1 has been classified as Green List (High Evidence).
Mendeliome v0.8730 ARIH1 Bryony Thompson gene: ARIH1 was added
gene: ARIH1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: ARIH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARIH1 were set to 29689197; 32102558
Phenotypes for gene: ARIH1 were set to Thoracic aortic aneurysm
Review for gene: ARIH1 was set to GREEN
Added comment: 3 unrelated families: A de novo case (R171*) with thoracic aortic aneurysm (TAA), and 2 siblings with TAA and a missense (E15Q). Another proband with cerebrovascular aneurysm (family history of TAA) and a missense variant (E44G). Supporting functional assays of the variants and a drosophila model.
Sources: Other
Mendeliome v0.8729 SLC41A1 Zornitza Stark Phenotypes for gene: SLC41A1 were changed from Nephronophthisis to Nephronophthisis-like nephropathy 2, MIM# 619468
Mendeliome v0.8728 SLC41A1 Zornitza Stark edited their review of gene: SLC41A1: Changed phenotypes: Nephronophthisis-like nephropathy 2, MIM# 619468
Mendeliome v0.8728 PRPF31 Zornitza Stark Marked gene: PRPF31 as ready
Mendeliome v0.8728 PRPF31 Zornitza Stark Gene: prpf31 has been classified as Green List (High Evidence).
Mendeliome v0.8728 PRPF31 Zornitza Stark Phenotypes for gene: PRPF31 were changed from to Retinitis pigmentosa 11, MIM#600138
Mendeliome v0.8727 PRPF31 Zornitza Stark Publications for gene: PRPF31 were set to
Mendeliome v0.8726 PRPF31 Zornitza Stark Mode of inheritance for gene: PRPF31 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8725 PRPF31 Zornitza Stark Tag SV/CNV tag was added to gene: PRPF31.
Mendeliome v0.8725 PRPF31 Zornitza Stark reviewed gene: PRPF31: Rating: GREEN; Mode of pathogenicity: None; Publications: 32014492; Phenotypes: Retinitis pigmentosa 11, MIM#600138; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8725 RNF168 Zornitza Stark Marked gene: RNF168 as ready
Mendeliome v0.8725 RNF168 Zornitza Stark Gene: rnf168 has been classified as Green List (High Evidence).
Mendeliome v0.8725 RNF168 Zornitza Stark Phenotypes for gene: RNF168 were changed from to RIDDLE syndrome MIM# 611943; Radiosensitivity; Immune Deficiency; Dysmorphic Features; Learning difficulties; Low IgG or IgA; Short stature; mild defect of motor control to ataxia; normal intelligence to learning difficulties; mild facial dysmorphism to microcephaly
Mendeliome v0.8724 RNF168 Zornitza Stark Publications for gene: RNF168 were set to
Mendeliome v0.8723 RNF168 Zornitza Stark Mode of inheritance for gene: RNF168 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8722 RFXAP Zornitza Stark Marked gene: RFXAP as ready
Mendeliome v0.8722 RFXAP Zornitza Stark Gene: rfxap has been classified as Green List (High Evidence).
Mendeliome v0.8722 RFXAP Zornitza Stark Phenotypes for gene: RFXAP were changed from to Bare lymphocyte syndrome, type II, complementation group D MIM# 209920; Low CD4+ T cells; reduced MHC II expression on lymphocytes; Normal-low Ig levels; Failure to thrive; respiratory/gastrointestinal infections; liver/biliary tract disease; diarrhoea; Severe autoimmune cytopaenia; agammaglobulinaemia
Mendeliome v0.8721 RFXAP Zornitza Stark Publications for gene: RFXAP were set to
Mendeliome v0.8720 RFXAP Zornitza Stark Mode of inheritance for gene: RFXAP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8719 RFXAP Zornitza Stark Tag founder tag was added to gene: RFXAP.
Mendeliome v0.8719 RFXANK Zornitza Stark Marked gene: RFXANK as ready
Mendeliome v0.8719 RFXANK Zornitza Stark Gene: rfxank has been classified as Green List (High Evidence).
Mendeliome v0.8719 RFXANK Zornitza Stark Phenotypes for gene: RFXANK were changed from to MHC class II deficiency, complementation group B MIM# 209920; Bare Lymphocyte Syndrome, type II, complementation group B; Low CD4+ T cells; reduced MHC II expression on lymphocytes; Normal-low Ig levels; Failure to thrive; respiratory/gastrointestinal infections; liver/biliary tract disease; diarrhoea; Severe autoimmune cytopaenia; agammaglobulinaemia
Mendeliome v0.8718 RFXANK Zornitza Stark Publications for gene: RFXANK were set to
Mendeliome v0.8717 RFXANK Zornitza Stark Tag founder tag was added to gene: RFXANK.
Mendeliome v0.8717 RFXANK Zornitza Stark Mode of inheritance for gene: RFXANK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8716 RBCK1 Zornitza Stark Marked gene: RBCK1 as ready
Mendeliome v0.8716 RBCK1 Zornitza Stark Gene: rbck1 has been classified as Green List (High Evidence).
Mendeliome v0.8716 RBCK1 Zornitza Stark Phenotypes for gene: RBCK1 were changed from to Polyglucosan body myopathy 1 with or without immunodeficiency MIM# 615895; muscular weakness; cardiomyopathy; recurrent bacterial/viral infections; autoinflammation; immunodeficiency; Poor antibody responses to polysaccharides; failure to thrive; fever; pneumonia
Mendeliome v0.8715 RBCK1 Zornitza Stark Publications for gene: RBCK1 were set to
Mendeliome v0.8714 RBCK1 Zornitza Stark Mode of inheritance for gene: RBCK1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8713 RFXANK Danielle Ariti reviewed gene: RFXANK: Rating: GREEN; Mode of pathogenicity: None; Publications: 12618906; Phenotypes: MHC class II deficiency, complementation group B MIM# 209920, Bare Lymphocyte Syndrome, type II, complementation group B, Low CD4+ T cells, reduced MHC II expression on lymphocytes, Normal-low Ig levels, Failure to thrive, respiratory/gastrointestinal infections, liver/biliary tract disease, diarrhoea, Severe autoimmune cytopaenia, agammaglobulinaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8713 RFXAP Danielle Ariti reviewed gene: RFXAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 9118943, 32875002, 11258423; Phenotypes: Bare lymphocyte syndrome, type II, complementation group D MIM# 209920, Low CD4+ T cells, reduced MHC II expression on lymphocytes, Normal-low Ig levels, Failure to thrive, respiratory/gastrointestinal infections, liver/biliary tract disease, diarrhoea, Severe autoimmune cytopaenia, agammaglobulinaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8713 RNF168 Danielle Ariti reviewed gene: RNF168: Rating: GREEN; Mode of pathogenicity: None; Publications: 19203578, 21394101, 29255463, 21552324; Phenotypes: RIDDLE syndrome MIM# 611943, Radiosensitivity, Immune Deficiency, Dysmorphic Features, Learning difficulties, Low IgG or IgA, Short stature, mild defect of motor control to ataxia, normal intelligence to learning difficulties, mild facial dysmorphism to microcephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8713 RBCK1 Danielle Ariti reviewed gene: RBCK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29260357, 29695863; Phenotypes: Polyglucosan body myopathy 1 with or without immunodeficiency MIM# 615895, muscular weakness, cardiomyopathy, recurrent bacterial/viral infections, autoinflammation, immunodeficiency, Poor antibody responses to polysaccharides, failure to thrive, fever, pneumonia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8713 ABCC2 Zornitza Stark Marked gene: ABCC2 as ready
Mendeliome v0.8713 ABCC2 Zornitza Stark Gene: abcc2 has been classified as Green List (High Evidence).
Mendeliome v0.8713 ABCC2 Zornitza Stark Phenotypes for gene: ABCC2 were changed from to Dubin-Johnson syndrome, MIM# 237500
Mendeliome v0.8712 ABCC2 Zornitza Stark Mode of inheritance for gene: ABCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8711 ABCC2 Zornitza Stark reviewed gene: ABCC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dubin-Johnson syndrome, MIM# 237500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8711 CLDN9 Bryony Thompson Publications for gene: CLDN9 were set to 31175426; 19696885
Mendeliome v0.8710 CLDN9 Bryony Thompson Classified gene: CLDN9 as Green List (high evidence)
Mendeliome v0.8710 CLDN9 Bryony Thompson Gene: cldn9 has been classified as Green List (High Evidence).
Mendeliome v0.8709 CLDN9 Bryony Thompson reviewed gene: CLDN9: Rating: GREEN; Mode of pathogenicity: None; Publications: 19696885, 31175426, 34265170; Phenotypes: Deafness, autosomal recessive 116 MIM#619093; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8709 UBR1 Zornitza Stark changed review comment from: >50 unrelated families reported, reviewed in PMID: 24599544.

Common clinical features include poor growth, mental retardation, and variable dysmorphic features, including aplasia or hypoplasia of the nasal alae, abnormal hair patterns or scalp defects, and oligodontia. Other features include hypothyroidism, sensorineural hearing loss, imperforate anus, and pancreatic exocrine insufficiency.; to: >50 unrelated families reported, reviewed in PMID: 24599544.

Common clinical features include poor growth, intellectual disability, and variable dysmorphic features, including aplasia or hypoplasia of the nasal alae, abnormal hair patterns or scalp defects, and oligodontia. Other features include hypothyroidism, sensorineural hearing loss, imperforate anus, and pancreatic exocrine insufficiency.
Mendeliome v0.8709 UBR1 Zornitza Stark Marked gene: UBR1 as ready
Mendeliome v0.8709 UBR1 Zornitza Stark Gene: ubr1 has been classified as Green List (High Evidence).
Mendeliome v0.8709 UBR1 Zornitza Stark Phenotypes for gene: UBR1 were changed from to Johanson-Blizzard syndrome (MIM#243800)
Mendeliome v0.8708 UBR1 Zornitza Stark Publications for gene: UBR1 were set to
Mendeliome v0.8707 UBR1 Zornitza Stark Mode of inheritance for gene: UBR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8706 UBR1 Zornitza Stark reviewed gene: UBR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24599544; Phenotypes: Johanson-Blizzard syndrome (MIM#243800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8706 ACTL6A Zornitza Stark Marked gene: ACTL6A as ready
Mendeliome v0.8706 ACTL6A Zornitza Stark Gene: actl6a has been classified as Green List (High Evidence).
Mendeliome v0.8706 ACTL6A Zornitza Stark Phenotypes for gene: ACTL6A were changed from to Intellectual disability
Mendeliome v0.8705 ACTL6A Zornitza Stark Publications for gene: ACTL6A were set to
Mendeliome v0.8704 ACTL6A Zornitza Stark Mode of inheritance for gene: ACTL6A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8703 ACTL6A Zornitza Stark changed review comment from: Two individuals from unrelated families reported with missense variants in this gene. Part of the BAF complex. Only one confirmed de novo.; to: Two individuals from unrelated families reported with missense variants in this gene, and one with a splice-site variant. Part of the BAF complex. Only one missense confirmed de novo, pathogenicity of the other variant uncertain.
PMID 31994175: fourth individual reported, recurrent de novo p.Arg377Trp
Mendeliome v0.8703 ACTL6A Zornitza Stark edited their review of gene: ACTL6A: Changed publications: 28649782, 31994175
Mendeliome v0.8703 VAV1 Zornitza Stark Marked gene: VAV1 as ready
Mendeliome v0.8703 VAV1 Zornitza Stark Gene: vav1 has been classified as Red List (Low Evidence).
Mendeliome v0.8703 VAV1 Zornitza Stark gene: VAV1 was added
gene: VAV1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: VAV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VAV1 were set to 20638113; 23058036
Phenotypes for gene: VAV1 were set to Common variable immnodeficiency
Review for gene: VAV1 was set to RED
Added comment: Reduced VAV1 expression has been reported in multiple T-CVID cases, however only one large deletion (exon 2-27) has been reported in a single case in a publication from 2012. The CNV was detected using real-time qPCR, but was not confirmed by an orthogonal method.
Sources: Expert Review
Mendeliome v0.8702 TCF3 Zornitza Stark Marked gene: TCF3 as ready
Mendeliome v0.8702 TCF3 Zornitza Stark Gene: tcf3 has been classified as Green List (High Evidence).
Mendeliome v0.8702 TCF3 Zornitza Stark Phenotypes for gene: TCF3 were changed from to Agammaglobulinaemia 8, autosomal dominant, MIM# 616941
Mendeliome v0.8701 TCF3 Zornitza Stark Publications for gene: TCF3 were set to
Mendeliome v0.8700 TCF3 Zornitza Stark Mode of inheritance for gene: TCF3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8699 TCF3 Zornitza Stark reviewed gene: TCF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24216514, 28532655, 30063982, 8001124, 8001125; Phenotypes: Agammaglobulinaemia 8, autosomal dominant, MIM# 616941; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8699 PRKCD Zornitza Stark Marked gene: PRKCD as ready
Mendeliome v0.8699 PRKCD Zornitza Stark Gene: prkcd has been classified as Green List (High Evidence).
Mendeliome v0.8699 PRKCD Zornitza Stark Phenotypes for gene: PRKCD were changed from to Autoimmune lymphoproliferative syndrome, type III, MIM# 615559; CVID 9
Mendeliome v0.8698 PRKCD Zornitza Stark Publications for gene: PRKCD were set to
Mendeliome v0.8697 PRKCD Zornitza Stark Mode of inheritance for gene: PRKCD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8696 PRKCD Zornitza Stark reviewed gene: PRKCD: Rating: GREEN; Mode of pathogenicity: None; Publications: 23319571, 23666743, 23430113, 11976687, 33047643, 29867916; Phenotypes: Autoimmune lymphoproliferative syndrome, type III, MIM# 615559, CVID 9; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8696 CD19 Zornitza Stark changed review comment from: More than 5 unrelated families reported.; to: More than 5 unrelated families reported. Clinical features include increased susceptibility to infection, hypogammaglobulinaemia, and normal numbers of mature B cells in blood, indicating a B-cell antibody-deficient immunodeficiency disorder.
Mendeliome v0.8696 CD19 Zornitza Stark Marked gene: CD19 as ready
Mendeliome v0.8696 CD19 Zornitza Stark Gene: cd19 has been classified as Green List (High Evidence).
Mendeliome v0.8696 CD19 Zornitza Stark Phenotypes for gene: CD19 were changed from to Immunodeficiency, common variable, 3, MIM# 613493
Mendeliome v0.8695 CD19 Zornitza Stark Publications for gene: CD19 were set to
Mendeliome v0.8694 CD19 Zornitza Stark Mode of inheritance for gene: CD19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8693 CD19 Zornitza Stark reviewed gene: CD19: Rating: GREEN; Mode of pathogenicity: None; Publications: 16672701, 17882224, 17882224, 21330302, 21159371; Phenotypes: Immunodeficiency, common variable, 3, MIM# 613493; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8693 SNRPB Zornitza Stark Marked gene: SNRPB as ready
Mendeliome v0.8693 SNRPB Zornitza Stark Gene: snrpb has been classified as Green List (High Evidence).
Mendeliome v0.8693 SNRPB Zornitza Stark Phenotypes for gene: SNRPB were changed from to Cerebrocostomandibular syndrome, MIM# 117650
Mendeliome v0.8692 SNRPB Zornitza Stark Publications for gene: SNRPB were set to
Mendeliome v0.8691 SNRPB Zornitza Stark Mode of inheritance for gene: SNRPB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8690 SNRPB Zornitza Stark Tag 5'UTR tag was added to gene: SNRPB.
Tag deep intronic tag was added to gene: SNRPB.
Mendeliome v0.8690 SNRPB Zornitza Stark reviewed gene: SNRPB: Rating: GREEN; Mode of pathogenicity: None; Publications: 25047197, 25504470, 26971886; Phenotypes: Cerebrocostomandibular syndrome, MIM# 117650; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8690 RBM10 Zornitza Stark Marked gene: RBM10 as ready
Mendeliome v0.8690 RBM10 Zornitza Stark Gene: rbm10 has been classified as Green List (High Evidence).
Mendeliome v0.8690 RBM10 Zornitza Stark Phenotypes for gene: RBM10 were changed from to TARP syndrome, MIM# 311900
Mendeliome v0.8689 RBM10 Zornitza Stark Publications for gene: RBM10 were set to
Mendeliome v0.8688 RBM10 Zornitza Stark Mode of inheritance for gene: RBM10 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8687 RBM10 Zornitza Stark reviewed gene: RBM10: Rating: GREEN; Mode of pathogenicity: None; Publications: 20451169, 24259342, 30450804, 30189253, 33340101; Phenotypes: TARP syndrome, MIM# 311900; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8687 IPO8 Zornitza Stark Phenotypes for gene: IPO8 were changed from Loeys-Dietz syndrome-like; cardiovascular, neurologic, skeletal and immunologic abnormalities to Vascular aneurysm, immune dysregulation, skeletal anomalies, and skin and joint laxity, MIM# 619472; Loeys-Dietz syndrome-like; cardiovascular, neurologic, skeletal and immunologic abnormalities
Mendeliome v0.8686 IPO8 Zornitza Stark edited their review of gene: IPO8: Changed phenotypes: Vascular aneurysm, immune dysregulation, skeletal anomalies, and skin and joint laxity, MIM# 619472, Loeys-Dietz syndrome-like, cardiovascular, neurologic, skeletal and immunologic abnormalities
Mendeliome v0.8686 OTX2 Zornitza Stark edited their review of gene: OTX2: Added comment: Three families reported with variants in OTX2 and otocyephaly-dysgnathia. Note variants were inherited in two of the families: in one family, from mother with microphthalmia (recognised OTX2 phenotype) and the other from an unaffected father. Lamb animal model reported.; Changed publications: 24167467, 25589041, 31969185; Changed phenotypes: Microphthalmia, syndromic 5, MIM# 610125, Pituitary hormone deficiency, combined, 6, MIM# 613986, Retinal dystrophy, early-onset, with or without pituitary dysfunction, MIM# 610125, Otocephaly-dysgnathia complex
Mendeliome v0.8686 POLR1D Zornitza Stark Marked gene: POLR1D as ready
Mendeliome v0.8686 POLR1D Zornitza Stark Gene: polr1d has been classified as Green List (High Evidence).
Mendeliome v0.8686 POLR1D Zornitza Stark Phenotypes for gene: POLR1D were changed from to Treacher Collins syndrome 2, MIM# 613717
Mendeliome v0.8685 POLR1D Zornitza Stark Publications for gene: POLR1D were set to
Mendeliome v0.8684 POLR1D Zornitza Stark Mode of inheritance for gene: POLR1D was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8683 POLR1D Zornitza Stark reviewed gene: POLR1D: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131976, 24603435, 27448281, 25790162; Phenotypes: Treacher Collins syndrome 2, MIM# 613717; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8683 TP73 Zornitza Stark Phenotypes for gene: TP73 were changed from Cortical malformation; Lissencephaly to Ciliary dyskinesia, primary, 47, and lissencephaly, MIM#619466; Cortical malformation; Lissencephaly
Mendeliome v0.8682 TP73 Zornitza Stark reviewed gene: TP73: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 47, and lissencephaly, MIM#619466; Mode of inheritance: None
Mendeliome v0.8682 SYT2 Zornitza Stark Phenotypes for gene: SYT2 were changed from Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040 to Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040; Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive MIM#619461
Mendeliome v0.8681 SYT2 Zornitza Stark edited their review of gene: SYT2: Changed phenotypes: Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040, Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive MIM#619461
Mendeliome v0.8681 POLR1C Zornitza Stark Marked gene: POLR1C as ready
Mendeliome v0.8681 POLR1C Zornitza Stark Gene: polr1c has been classified as Green List (High Evidence).
Mendeliome v0.8681 POLR1C Zornitza Stark Phenotypes for gene: POLR1C were changed from to Treacher Collins syndrome 3, MIM# 248390; Leukodystrophy, hypomyelinating, 11, MIM# 616494
Mendeliome v0.8680 POLR1C Zornitza Stark Publications for gene: POLR1C were set to
Mendeliome v0.8679 POLR1C Zornitza Stark Mode of inheritance for gene: POLR1C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8678 POLR1C Zornitza Stark reviewed gene: POLR1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131976, 30957429, 26151409, 32042905; Phenotypes: Treacher Collins syndrome 3, MIM# 248390, Leukodystrophy, hypomyelinating, 11, MIM# 616494; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8678 SF3B4 Zornitza Stark Marked gene: SF3B4 as ready
Mendeliome v0.8678 SF3B4 Zornitza Stark Gene: sf3b4 has been classified as Green List (High Evidence).
Mendeliome v0.8678 SF3B4 Zornitza Stark Phenotypes for gene: SF3B4 were changed from to Acrofacial dysostosis 1, Nager type, MIM# 154400
Mendeliome v0.8677 SF3B4 Zornitza Stark Publications for gene: SF3B4 were set to
Mendeliome v0.8676 SF3B4 Zornitza Stark Mode of inheritance for gene: SF3B4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8675 SF3B4 Zornitza Stark reviewed gene: SF3B4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22541558, 23568615, 24003905; Phenotypes: Acrofacial dysostosis 1, Nager type, MIM# 154400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8675 TMCO1 Zornitza Stark Marked gene: TMCO1 as ready
Mendeliome v0.8675 TMCO1 Zornitza Stark Gene: tmco1 has been classified as Green List (High Evidence).
Mendeliome v0.8675 TMCO1 Zornitza Stark Phenotypes for gene: TMCO1 were changed from to Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, MIM# 213980
Mendeliome v0.8674 TMCO1 Zornitza Stark Publications for gene: TMCO1 were set to
Mendeliome v0.8673 TMCO1 Zornitza Stark Mode of inheritance for gene: TMCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8672 TMCO1 Zornitza Stark reviewed gene: TMCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20018682, 23320496, 17351359, 30556256, 31102500; Phenotypes: Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, MIM# 213980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8672 SEMA3D Zornitza Stark Phenotypes for gene: SEMA3D were changed from Hand and foot malformations to Hand and foot malformations; Hirschsprung disease
Mendeliome v0.8671 SPTBN4 Zornitza Stark reviewed gene: SPTBN4: Rating: GREEN; Mode of pathogenicity: None; Publications: 33772159, 29861105; Phenotypes: Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, MIM# 617519; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8671 RGS10 Zornitza Stark Marked gene: RGS10 as ready
Mendeliome v0.8671 RGS10 Zornitza Stark Gene: rgs10 has been classified as Red List (Low Evidence).
Mendeliome v0.8671 RGS10 Zornitza Stark gene: RGS10 was added
gene: RGS10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RGS10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS10 were set to 34315806; 34339853
Phenotypes for gene: RGS10 were set to Immunodeficiency; short stature
Review for gene: RGS10 was set to RED
Added comment: Three affected siblings with short stature and immunodeficiency and segregating biallelic variants in RGS10 (c.489_491del:p.E163del and c.G511T:p.A171S). The affected individuals had recurrent infections, hypergammaglobulinaemia, profoundly reduced lymphocyte chemotaxis, abnormal lymph node architecture, and short stature due to growth hormone deficiency. Limited functional data presented. Further experimental data linking RGS10 to immune function presented in PMID 34339853.
Sources: Literature
Mendeliome v0.8670 MAST3 Zornitza Stark Marked gene: MAST3 as ready
Mendeliome v0.8670 MAST3 Zornitza Stark Gene: mast3 has been classified as Green List (High Evidence).
Mendeliome v0.8670 MAST3 Zornitza Stark Classified gene: MAST3 as Green List (high evidence)
Mendeliome v0.8670 MAST3 Zornitza Stark Gene: mast3 has been classified as Green List (High Evidence).
Mendeliome v0.8669 MAST3 Zornitza Stark gene: MAST3 was added
gene: MAST3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAST3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST3 were set to 34185323
Phenotypes for gene: MAST3 were set to Developmental and epileptic encephalopathy
Review for gene: MAST3 was set to GREEN
Added comment: Eleven individuals reported with de novo missense variants in the STK domain, including two recurrent variants p.G510S (n = 5) and p.G515S (n = 3). All 11 individuals had developmental and epileptic encephalopathy, with 8 having normal development prior to seizure onset at <2 years of age. All patients developed multiple seizure types, 9 of 11 patients had seizures triggered by fever and 9 of 11 patients had drug-resistant seizures. Limited functional data.
Sources: Literature
Mendeliome v0.8668 SF3B2 Zornitza Stark Marked gene: SF3B2 as ready
Mendeliome v0.8668 SF3B2 Zornitza Stark Gene: sf3b2 has been classified as Green List (High Evidence).
Mendeliome v0.8668 SF3B2 Zornitza Stark Classified gene: SF3B2 as Green List (high evidence)
Mendeliome v0.8668 SF3B2 Zornitza Stark Gene: sf3b2 has been classified as Green List (High Evidence).
Mendeliome v0.8667 SF3B2 Zornitza Stark gene: SF3B2 was added
gene: SF3B2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SF3B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SF3B2 were set to 34344887
Phenotypes for gene: SF3B2 were set to Craniofacial microsomia
Review for gene: SF3B2 was set to GREEN
Added comment: Twenty individuals from seven families reported with de novo or transmitted haploinsufficient variants in SF3B2. Affected individuals had mandibular hypoplasia, microtia, facial and preauricular tags, epibulbar dermoids, lateral oral clefts in addition to skeletal and cardiac abnormalities.

Targeted morpholino knockdown of SF3B2 in Xenopus resulted in disruption of cranial neural crest precursor formation and subsequent craniofacial cartilage defects, supporting a link between spliceosome mutations and impaired neural crest development in congenital craniofacial disease.

The families were ascertained from a cohort and the authors suggest that haploinsufficient variants in SF3B2 are the most prevalent genetic cause of CFM, explaining ~3% of sporadic and ~25% of familial cases.
Sources: Literature
Mendeliome v0.8666 IMPG1 Zornitza Stark Marked gene: IMPG1 as ready
Mendeliome v0.8666 IMPG1 Zornitza Stark Gene: impg1 has been classified as Green List (High Evidence).
Mendeliome v0.8666 IMPG1 Zornitza Stark Phenotypes for gene: IMPG1 were changed from to Macular dystrophy, vitelliform, 4, OMIM:616151; Retinitis pigmentosa, MONDO:0019200
Mendeliome v0.8665 IMPG1 Zornitza Stark Publications for gene: IMPG1 were set to
Mendeliome v0.8664 IMPG1 Zornitza Stark Mode of inheritance for gene: IMPG1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8663 IMPG1 Arina Puzriakova reviewed gene: IMPG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23993198, 28644393, 30589393, 30688845, 32817297; Phenotypes: Macular dystrophy, vitelliform, 4, OMIM:616151, Retinitis pigmentosa, MONDO:0019200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8663 IFT172 Zornitza Stark Phenotypes for gene: IFT172 were changed from Retinitis pigmentosa 71 616394; Short-rib thoracic dysplasia 10 with or without polydactyly - 615630; Bardet-Biedl syndrome to Retinitis pigmentosa 71 616394; Short-rib thoracic dysplasia 10 with or without polydactyly - 615630; Bardet-Biedl syndrome 20, MIM# 619471
Mendeliome v0.8662 TRIM8 Zornitza Stark Phenotypes for gene: TRIM8 were changed from Intellectual disability; Seizures to Focal segmental glomerulosclerosis and neurodevelopmental syndrome, MIM# 619428; Intellectual disability; Seizures
Mendeliome v0.8661 TRIM8 Zornitza Stark edited their review of gene: TRIM8: Changed phenotypes: Focal segmental glomerulosclerosis and neurodevelopmental syndrome, MIM# 619428, Intellectual disability, Seizures
Mendeliome v0.8661 CUL7 Zornitza Stark Marked gene: CUL7 as ready
Mendeliome v0.8661 CUL7 Zornitza Stark Gene: cul7 has been classified as Green List (High Evidence).
Mendeliome v0.8661 CUL7 Zornitza Stark Phenotypes for gene: CUL7 were changed from to 3-M syndrome 1, MIM# 273750; Yakut short stature syndrome
Mendeliome v0.8660 CUL7 Zornitza Stark Publications for gene: CUL7 were set to
Mendeliome v0.8659 CUL7 Zornitza Stark Mode of inheritance for gene: CUL7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8658 CUL7 Zornitza Stark reviewed gene: CUL7: Rating: GREEN; Mode of pathogenicity: None; Publications: 16142236, 19225462, 17675530; Phenotypes: 3-M syndrome 1, MIM# 273750, Yakut short stature syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8658 ACAN Zornitza Stark Publications for gene: ACAN were set to
Mendeliome v0.8657 ACAN Zornitza Stark edited their review of gene: ACAN: Added comment: Patients with SSOAD exhibit a broad phenotypic spectrum involving short stature associated with advanced bone maturation and early-onset osteoarthritis (OA), as well as mild dysmorphic features consisting of midface hypoplasia, brachydactyly, broad great toes, and lumbar lordosis. Other features include intervertebral disc disease and osteochondritis dissecans, which is characterized by separation of articular cartilage and subchondral bone from the articular surface. Phenotypes are highly variable even among patients within the same family, and there are no apparent genotype-phenotype correlations.

Well established gene-disease association, multiple families reported.

Note fewer families reported with bi-allelic variants in this gene and extreme short stature.; Changed publications: 24762113, 27870580, 19110214, 30124491, 28331218, 20137779; Changed phenotypes: Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans, OMIM# 165800, Spondyloepimetaphyseal dysplasia, aggrecan type 612813
Mendeliome v0.8657 NFKBIA Zornitza Stark Marked gene: NFKBIA as ready
Mendeliome v0.8657 NFKBIA Zornitza Stark Gene: nfkbia has been classified as Green List (High Evidence).
Mendeliome v0.8657 NFKBIA Zornitza Stark Phenotypes for gene: NFKBIA were changed from to Ectodermal dysplasia and immunodeficiency 2 MIM# 612132; Ectodermal dysplasia; TCR/ BCR activation impaired; low memory and isotype switched B cells; decreased IgG and IgA; elevated IgM; poor specific antibody responses; diarrhoea; agammaglobulinaemia; ectodermal dysplasia; recurrent respiratory and gastrointestinal infections; colitis; variable defects of skin, hair and teeth
Mendeliome v0.8656 NFKBIA Zornitza Stark Mode of pathogenicity for gene: NFKBIA was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v0.8655 NFKBIA Zornitza Stark Mode of inheritance for gene: NFKBIA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8654 NFKB2 Zornitza Stark Marked gene: NFKB2 as ready
Mendeliome v0.8654 NFKB2 Zornitza Stark Gene: nfkb2 has been classified as Green List (High Evidence).
Mendeliome v0.8654 NFKB2 Zornitza Stark Phenotypes for gene: NFKB2 were changed from to Immunodeficiency, common variable, 10 MIM# 615577; Low serum IgG, IgA, IgM; low B cell numbers; low switched memory B cells; Recurrent sinopulmonary infections, Alopecia; endocrinopathies; ACTH deficiency
Mendeliome v0.8653 NFKB2 Zornitza Stark Publications for gene: NFKB2 were set to
Mendeliome v0.8652 NFKB2 Zornitza Stark Mode of inheritance for gene: NFKB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8651 NFKB1 Zornitza Stark Marked gene: NFKB1 as ready
Mendeliome v0.8651 NFKB1 Zornitza Stark Gene: nfkb1 has been classified as Green List (High Evidence).
Mendeliome v0.8651 NFKB1 Zornitza Stark Phenotypes for gene: NFKB1 were changed from to Immunodeficiency, common variable, 12 MIM# 616576; Normal-low IgG, IgA, IgM; low-normal B cells; low switched memory B cells; hypogammaglobulinaemia; recurrent respiratory and gastrointestinal infections; Chronic obstructive pulmonary disease COPD; EBV proliferation; autoimmunity; alopecia
Mendeliome v0.8650 NFKB1 Zornitza Stark Publications for gene: NFKB1 were set to
Mendeliome v0.8649 NFKB1 Zornitza Stark Mode of inheritance for gene: NFKB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8648 MCM4 Zornitza Stark Marked gene: MCM4 as ready
Mendeliome v0.8648 MCM4 Zornitza Stark Gene: mcm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8648 MCM4 Zornitza Stark Phenotypes for gene: MCM4 were changed from to Immunodeficiency 54 MIM# 609981; Decreased NK cell number and function; Viral infections (EBV, HSV, VZV); Short stature; B cell lymphoma; Adrenal failure; Failure to thrive; Microcephaly; Increased chromosomal breakage; Hyperpigmentation; Lymphadenopathy
Mendeliome v0.8647 MCM4 Zornitza Stark Publications for gene: MCM4 were set to
Mendeliome v0.8646 MCM4 Zornitza Stark Mode of inheritance for gene: MCM4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8645 MCM4 Zornitza Stark Classified gene: MCM4 as Amber List (moderate evidence)
Mendeliome v0.8645 MCM4 Zornitza Stark Gene: mcm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8644 MCM4 Zornitza Stark Tag founder tag was added to gene: MCM4.
Mendeliome v0.8644 MCM4 Zornitza Stark reviewed gene: MCM4: Rating: AMBER; Mode of pathogenicity: None; Publications: 22354167, 22354170, 22499342; Phenotypes: Immunodeficiency 54 MIM# 609981, Decreased NK cell number and function, Viral infections (EBV, HSV, VZV), Short stature, B cell lymphoma, Adrenal failure, Failure to thrive, Microcephaly, Increased chromosomal breakage, Hyperpigmentation, Lymphadenopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8644 MAP3K14 Zornitza Stark Marked gene: MAP3K14 as ready
Mendeliome v0.8644 MAP3K14 Zornitza Stark Gene: map3k14 has been classified as Green List (High Evidence).
Mendeliome v0.8644 MAP3K14 Zornitza Stark Phenotypes for gene: MAP3K14 were changed from to NIK deficiency; Poor T cell proliferation to antigen; Low B-cell numbers; Low NK number and function; recurrent bacterial/viral/ cryptosporidium infections; hypogammaglobulinaemia; decreased immunoglobulin levels
Mendeliome v0.8643 MAP3K14 Zornitza Stark Publications for gene: MAP3K14 were set to
Mendeliome v0.8642 MAP3K14 Zornitza Stark Mode of inheritance for gene: MAP3K14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8641 MAP3K14 Zornitza Stark reviewed gene: MAP3K14: Rating: GREEN; Mode of pathogenicity: None; Publications: 10319865, 11238593, 12352969; Phenotypes: NIK deficiency, Poor T cell proliferation to antigen, Low B-cell numbers, Low NK number and function, recurrent bacterial/viral/ cryptosporidium infections, hypogammaglobulinaemia, decreased immunoglobulin levels; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8641 LRBA Zornitza Stark Marked gene: LRBA as ready
Mendeliome v0.8641 LRBA Zornitza Stark Gene: lrba has been classified as Green List (High Evidence).
Mendeliome v0.8641 LRBA Zornitza Stark Phenotypes for gene: LRBA were changed from to Immunodeficiency, common variable, 8, with autoimmunity MIM# 614700; Normal-decreased CD4 numbers; T cell dysregulation; Low-normal B cells; Reduced IgG and IgA; Recurrent infections; chronic diarrhoea; inflammatory bowel disease; hypogammaglobulinaemia; pneumonitis; autoimmune disorders; thrombocytopaenia
Mendeliome v0.8640 LRBA Zornitza Stark Publications for gene: LRBA were set to
Mendeliome v0.8639 LRBA Zornitza Stark Mode of inheritance for gene: LRBA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8638 LRBA Zornitza Stark reviewed gene: LRBA: Rating: GREEN; Mode of pathogenicity: None; Publications: 22608502, 22721650, 25468195, 26206937, 33155142; Phenotypes: Immunodeficiency, common variable, 8, with autoimmunity MIM# 614700, Normal-decreased CD4 numbers, T cell dysregulation, Low-normal B cells, Reduced IgG and IgA, Recurrent infections, chronic diarrhoea, inflammatory bowel disease, hypogammaglobulinaemia, pneumonitis, autoimmune disorders, thrombocytopaenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8638 NFKBIA Danielle Ariti reviewed gene: NFKBIA: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 28597146, 23864385, 23708964; Phenotypes: Ectodermal dysplasia and immunodeficiency 2 MIM# 612132, Ectodermal dysplasia, TCR/ BCR activation impaired, low memory and isotype switched B cells, decreased IgG and IgA, elevated IgM, poor specific antibody responses, diarrhoea, agammaglobulinaemia, ectodermal dysplasia, recurrent respiratory and gastrointestinal infections, colitis, variable defects of skin, hair and teeth; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8638 NFKB2 Danielle Ariti reviewed gene: NFKB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24140114, 24888602, 25524009, 31417880; Phenotypes: Immunodeficiency, common variable, 10 MIM# 615577, Low serum IgG, IgA, IgM, low B cell numbers, low switched memory B cells, Recurrent sinopulmonary infections, Alopecia, endocrinopathies, ACTH deficiency; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8638 NFKB1 Danielle Ariti reviewed gene: NFKB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26279205, 32278790, 27022143, 7834752; Phenotypes: Immunodeficiency, common variable, 12 MIM# 616576, Normal-low IgG, IgA, IgM, low-normal B cells, low switched memory B cells, hypogammaglobulinaemia, recurrent respiratory and gastrointestinal infections, Chronic obstructive pulmonary disease COPD, EBV proliferation, autoimmunity, alopecia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8638 AQP2 Zornitza Stark Marked gene: AQP2 as ready
Mendeliome v0.8638 AQP2 Zornitza Stark Gene: aqp2 has been classified as Green List (High Evidence).
Mendeliome v0.8638 AQP2 Zornitza Stark Phenotypes for gene: AQP2 were changed from to Diabetes insipidus, nephrogenic, MIM#125800
Mendeliome v0.8637 AQP2 Zornitza Stark Publications for gene: AQP2 were set to
Mendeliome v0.8636 AQP2 Zornitza Stark Mode of inheritance for gene: AQP2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8635 AQP2 Zornitza Stark reviewed gene: AQP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 7537761, 11536078; Phenotypes: Diabetes insipidus, nephrogenic, MIM#125800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8635 RNF2 Zornitza Stark Phenotypes for gene: RNF2 were changed from epilepsy; intellectual disability; intrauterine growth retardation to Lou-Schoch-Yamamoto syndrome , MIM#619460; epilepsy; intellectual disability; intrauterine growth retardation
Mendeliome v0.8634 RNF2 Zornitza Stark reviewed gene: RNF2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Lou-Schoch-Yamamoto syndrome , MIM#619460; Mode of inheritance: None
Mendeliome v0.8634 USP7 Zornitza Stark Phenotypes for gene: USP7 were changed from Hao-Fountain syndrome, MIM# 616863; Intellectual disability; Autism to Hao-Fountain syndrome, MIM# 616863; MONDO:0014805; Intellectual disability; Autism
Mendeliome v0.8633 USP7 Zornitza Stark edited their review of gene: USP7: Changed phenotypes: Hao-Fountain syndrome, MIM# 616863, MONDO:0014805, Intellectual disability, Autism
Mendeliome v0.8633 GIMAP5 Zornitza Stark Marked gene: GIMAP5 as ready
Mendeliome v0.8633 GIMAP5 Zornitza Stark Gene: gimap5 has been classified as Green List (High Evidence).
Mendeliome v0.8633 GIMAP5 Zornitza Stark Classified gene: GIMAP5 as Green List (high evidence)
Mendeliome v0.8633 GIMAP5 Zornitza Stark Gene: gimap5 has been classified as Green List (High Evidence).
Mendeliome v0.8632 GIMAP5 Zornitza Stark gene: GIMAP5 was added
gene: GIMAP5 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: GIMAP5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GIMAP5 were set to 33956074
Phenotypes for gene: GIMAP5 were set to Portal hypertension, noncirrhotic, 2, MIM# 619463
Review for gene: GIMAP5 was set to GREEN
Added comment: 8 individuals from 4 unrelated families reported with onset of disease in the first decade of life. Clinical features included jaundice, hyperbilirubinaemia, pancytopaenia, including neutropaenia, lymphopaenia, and thrombocytopaenia, hepatosplenomegaly, and oesophageal varices. Some individuals had recurrent infections or features suggestive of an immunodeficiency. Liver biopsy was notable for the absence of cirrhosis and the presence of nodular regeneration.
Sources: Expert list
Mendeliome v0.8631 ERBB2 Zornitza Stark Phenotypes for gene: ERBB2 were changed from to Visceral neuropathy, familial, 2, autosomal recessive, MIM# 619465
Mendeliome v0.8630 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis; Complex neurocristinopathy to Lethal congenital contractural syndrome 2, MIM# 607598; Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Hirschsprung disease; Arthrogryposis; Complex neurocristinopathy
Mendeliome v0.8629 ERBB3 Zornitza Stark edited their review of gene: ERBB3: Changed phenotypes: Lethal congenital contractural syndrome 2, MIM# 607598, Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180, Complex neurocristinopathy
Mendeliome v0.8629 IL7R Zornitza Stark Marked gene: IL7R as ready
Mendeliome v0.8629 IL7R Zornitza Stark Gene: il7r has been classified as Green List (High Evidence).
Mendeliome v0.8629 IL7R Zornitza Stark Phenotypes for gene: IL7R were changed from to Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type MIM# 608971; fever; rash; failure to thrive; recurrent respiratory and gastric infections; diarrhoea; lymphadenopathy; pneumonitis; Pancytopaenia; low T-cell numbers; decreased immunoglobulins; normal-high B/NK-cell numbers.
Mendeliome v0.8628 IL7R Zornitza Stark Publications for gene: IL7R were set to
Mendeliome v0.8627 IL7R Zornitza Stark Mode of inheritance for gene: IL7R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8626 MALT1 Zornitza Stark Marked gene: MALT1 as ready
Mendeliome v0.8626 MALT1 Zornitza Stark Gene: malt1 has been classified as Green List (High Evidence).
Mendeliome v0.8626 MALT1 Zornitza Stark Phenotypes for gene: MALT1 were changed from to Immunodeficiency 12 MIM# 615468; poor T-cell proliferation; normal T/B cell numbers; poor specific antibody response; recurrent bacterial/fungal/viral infections; bronchiectasis; failure to thrive
Mendeliome v0.8625 MALT1 Zornitza Stark Publications for gene: MALT1 were set to
Mendeliome v0.8624 MALT1 Zornitza Stark Mode of inheritance for gene: MALT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8623 IL2RG Zornitza Stark Marked gene: IL2RG as ready
Mendeliome v0.8623 IL2RG Zornitza Stark Gene: il2rg has been classified as Green List (High Evidence).
Mendeliome v0.8623 IL2RG Zornitza Stark Phenotypes for gene: IL2RG were changed from to Combined immunodeficiency, X-linked, moderate MIM# 312863; Severe combined immunodeficiency, X-linked MIM# 300400; recurrent viral/fungal/bacterial infections; Low T/NK cells; Low Ig levels; lymphocytopaenia; hypogammaglobulinaemia; failure to thrive; diarrhoea; Pneumonia; Thymic hypoplasia
Mendeliome v0.8622 IL2RG Zornitza Stark Publications for gene: IL2RG were set to
Mendeliome v0.8621 IL2RG Zornitza Stark Mode of inheritance for gene: IL2RG was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8620 IL2RG Zornitza Stark reviewed gene: IL2RG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301584, 8462096, 8401490, 7883965, 9399950; Phenotypes: Combined immunodeficiency, X-linked, moderate MIM# 312863, Severe combined immunodeficiency, X-linked MIM# 300400, recurrent viral/fungal/bacterial infections, Low T/NK cells, Low Ig levels, lymphocytopaenia, hypogammaglobulinaemia, failure to thrive, diarrhoea, Pneumonia, Thymic hypoplasia; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8620 IKZF1 Zornitza Stark Marked gene: IKZF1 as ready
Mendeliome v0.8620 IKZF1 Zornitza Stark Gene: ikzf1 has been classified as Green List (High Evidence).
Mendeliome v0.8620 IKZF1 Zornitza Stark Phenotypes for gene: IKZF1 were changed from to Immunodeficiency, common variable, 13 MIM# 616873; recurrent bacterial respiratory infections; Thrombocytopaenia; immunodeficiency; Hypogammaglobulinaemia; decrease B-cells; decrease B-cell differentiation; decrease memory B/T cells; Low Ig; pneumocystis early CID onset
Mendeliome v0.8619 IKZF1 Zornitza Stark Publications for gene: IKZF1 were set to
Mendeliome v0.8618 IKZF1 Zornitza Stark Mode of inheritance for gene: IKZF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8617 IKZF1 Zornitza Stark reviewed gene: IKZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21548011, 26981933, 29889099, 31057532, 7923373, 11805317; Phenotypes: Immunodeficiency, common variable, 13 MIM# 616873, recurrent bacterial respiratory infections, Thrombocytopaenia, immunodeficiency, Hypogammaglobulinaemia, decrease B-cells, decrease B-cell differentiation, decrease memory B/T cells, Low Ig, pneumocystis early CID onset; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8617 ITK Zornitza Stark Marked gene: ITK as ready
Mendeliome v0.8617 ITK Zornitza Stark Gene: itk has been classified as Green List (High Evidence).
Mendeliome v0.8617 ITK Zornitza Stark Phenotypes for gene: ITK were changed from to Lymphoproliferative syndrome 1 MIM# 613011; Lymphadenopathy; Recurrent infections; Hypogammaglobulinaemia; Evidence of EBV infection; EBV associated B cell Lymphoproliferation; High EBV viral load; Normal-low serum Ig; Depleted CD4+ T cells; Anaemia; Thrombocytopaenia; Hepatosplenomegaly
Mendeliome v0.8616 ITK Zornitza Stark Publications for gene: ITK were set to
Mendeliome v0.8615 ITK Zornitza Stark Mode of inheritance for gene: ITK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8614 MALT1 Danielle Ariti Deleted their comment
Mendeliome v0.8614 MALT1 Danielle Ariti edited their review of gene: MALT1: Added comment: 5 individuals from 3 unrelated families with immunodeficiency phenotype have reported variants in MALT1; two MALT1-knockout mouse models displaying primary T- and B-cell lymphocyte deficiency.

Variants identified were homozygous missense variants resulting in the alteration of highly conserved residue domains.

All individuals reported onset in infancy of recurrent bacterial/ fungal/ viral infections leading to bronchiectasis and poor T-cell proliferation.; Changed rating: GREEN
Mendeliome v0.8614 IL7R Danielle Ariti reviewed gene: IL7R: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843216, 19890784, 26123418, 11023514, 7964471; Phenotypes: Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type MIM# 608971, fever, rash, failure to thrive, recurrent respiratory and gastric infections, diarrhoea, lymphadenopathy, pneumonitis, Pancytopaenia, low T-cell numbers, decreased immunoglobulins, normal-high B/NK-cell numbers.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8614 ITK Danielle Ariti reviewed gene: ITK: Rating: GREEN; Mode of pathogenicity: None; Publications: 19425169, 22289921, 25061172, 26056787, 9311799, 10213685; Phenotypes: Lymphoproliferative syndrome 1 MIM# 613011, Lymphadenopathy, Recurrent infections, Hypogammaglobulinaemia, Evidence of EBV infection, EBV associated B cell Lymphoproliferation, High EBV viral load, Normal-low serum Ig, Depleted CD4+ T cells, Anaemia, Thrombocytopaenia, Hepatosplenomegaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8614 MALT1 Danielle Ariti reviewed gene: MALT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23727036, 24332264, 14576442, 31037583; Phenotypes: Immunodeficiency 12 MIM# 615468, poor T-cell proliferation, normal T/B cell numbers, poor specific antibody response, recurrent bacterial/fungal/viral infections, bronchiectasis, failure to thrive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8614 PLCB4 Zornitza Stark Marked gene: PLCB4 as ready
Mendeliome v0.8614 PLCB4 Zornitza Stark Gene: plcb4 has been classified as Green List (High Evidence).
Mendeliome v0.8614 PLCB4 Zornitza Stark Phenotypes for gene: PLCB4 were changed from to Auriculocondylar syndrome 2, MIM# 614669
Mendeliome v0.8613 PLCB4 Zornitza Stark Publications for gene: PLCB4 were set to
Mendeliome v0.8612 PLCB4 Zornitza Stark Mode of inheritance for gene: PLCB4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8611 PLCB4 Zornitza Stark reviewed gene: PLCB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22560091, 23315542, 33131036, 32201334, 28328130, 27007857, 23913798; Phenotypes: Auriculocondylar syndrome 2, MIM# 614669; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8611 PBX1 Zornitza Stark Marked gene: PBX1 as ready
Mendeliome v0.8611 PBX1 Zornitza Stark Gene: pbx1 has been classified as Green List (High Evidence).
Mendeliome v0.8611 PBX1 Zornitza Stark Phenotypes for gene: PBX1 were changed from to Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, MIM# 617641
Mendeliome v0.8610 PBX1 Zornitza Stark Publications for gene: PBX1 were set to
Mendeliome v0.8609 PBX1 Zornitza Stark Mode of inheritance for gene: PBX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8608 PBX1 Zornitza Stark reviewed gene: PBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28566479, 29036646; Phenotypes: Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, MIM# 617641; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8608 VRK1 Zornitza Stark Phenotypes for gene: VRK1 were changed from Pontocerebellar hypoplasia type 1A, MIM# 607596; SMA to Pontocerebellar hypoplasia type 1A, MIM# 607596; Adult-onset spinal muscular atrophy without pontocerebellar hypoplasia
Mendeliome v0.8607 VRK1 Zornitza Stark Publications for gene: VRK1 were set to 19646678; 21937992; 25609612; 24126608; 27281532
Mendeliome v0.8606 VRK1 Zornitza Stark changed review comment from: Complex phenotype with mixed peripheral and central neurological features. Two families reported where PCH was prominent and accompanied by ataxia. At least three families also reported where peripheral neuropathy dominated the clinical picture without PCH/ataxia.; to: Complex phenotype with mixed peripheral and central neurological features. Two families reported where PCH was prominent and accompanied by ataxia. At least three families also reported where peripheral neuropathy dominated the clinical picture without PCH/ataxia.

Further delineation of phenotype 2021:
PMID 34169149: expanding spectrum of neurologic disorders associated with VRK1. Two Hispanic individuals, one homozygous (R321C: VUS and LP/P in ClinVar) and one cHet (R321C+V236M, latter P and more recently VUS in ClinVar), with slowly progressive weakness and a clinical syndrome consistent with adult-onset spinal muscular atrophy WITHOUT pontocerebellar atrophy. No hom in gnomAD and both have been reported in cHet individuals with other features: R321C in association with adult-onset amyotrophic lateral sclerosis and V236M with rapidly progressive sensorimotor polyneuropathy and microcephaly. Authors suggest PMID 26583493 and 31837156 have similar reports. PMID 26583493 reports a 32yo Hispanic individual, cHet H119R+R321C, with early-onset amyotrophic lateral sclerosis, 5 years progressive weakness. PMID 31837156 reports two patients with adult-onset length-dependent motor neuropathy from unrelated consanguineous families of Moroccan Jewish descent, both hom for R387H.
Mendeliome v0.8606 VRK1 Zornitza Stark edited their review of gene: VRK1: Changed publications: 19646678, 21937992, 25609612, 24126608, 27281532, 34169149, 26583493; Changed phenotypes: Pontocerebellar hypoplasia type 1A, MIM# 607596, Adult-onset spinal muscular atrophy without pontocerebellar hypoplasia
Mendeliome v0.8606 CLCN3 Zornitza Stark Marked gene: CLCN3 as ready
Mendeliome v0.8606 CLCN3 Zornitza Stark Gene: clcn3 has been classified as Green List (High Evidence).
Mendeliome v0.8606 CLCN3 Zornitza Stark Mode of inheritance for gene: CLCN3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.8605 CLCN3 Zornitza Stark Classified gene: CLCN3 as Green List (high evidence)
Mendeliome v0.8605 CLCN3 Zornitza Stark Gene: clcn3 has been classified as Green List (High Evidence).
Mendeliome v0.8604 TNPO2 Zornitza Stark Marked gene: TNPO2 as ready
Mendeliome v0.8604 TNPO2 Zornitza Stark Gene: tnpo2 has been classified as Green List (High Evidence).
Mendeliome v0.8604 TNPO2 Zornitza Stark Phenotypes for gene: TNPO2 were changed from Developmental delays, neurologic deficits and dysmorphic features to Intellectual disability, neurologic deficits and dysmorphic features
Mendeliome v0.8603 TNPO2 Zornitza Stark Classified gene: TNPO2 as Green List (high evidence)
Mendeliome v0.8603 TNPO2 Zornitza Stark Gene: tnpo2 has been classified as Green List (High Evidence).
Mendeliome v0.8602 ZDHHC15 Daniel Flanagan reviewed gene: ZDHHC15: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: cerebral palsy, intellectual disability, autism spectrum disorder, epilepsy; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8602 DNAH10 Zornitza Stark Marked gene: DNAH10 as ready
Mendeliome v0.8602 DNAH10 Zornitza Stark Gene: dnah10 has been classified as Green List (High Evidence).
Mendeliome v0.8602 DNAH10 Zornitza Stark Classified gene: DNAH10 as Green List (high evidence)
Mendeliome v0.8602 DNAH10 Zornitza Stark Gene: dnah10 has been classified as Green List (High Evidence).
Mendeliome v0.8601 CLCN3 Kristin Rigbye gene: CLCN3 was added
gene: CLCN3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CLCN3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CLCN3 were set to PMID: 34186028
Phenotypes for gene: CLCN3 were set to Neurodevelopmental disorder
Mode of pathogenicity for gene: CLCN3 was set to Other
Review for gene: CLCN3 was set to GREEN
Added comment: 11 individuals reported, 9 that carried 8 different rare heterozygous missense variants in CLCN3, and 2 siblings that were homozygous for an NMD-predicted frameshift variant likely abolishing ClC-3 function. All missense variants were confirmed to be de novo in eight individuals for whom parental data was available.

The 11 individuals in the cohort share clinical features of variable severity. All 11 have GDD or ID and dysmorphic features, and a majority has mood or behavioural disorders and structural brain abnormalities:
- Structural brain abnormalities on MRI (9/11) included partial or full agenesis of the corpus callosum (6/9), disorganized cerebellar folia (4/9), delayed myelination (3/9), decreased white matter volume (3/9), pons hypoplasia (3/9), and dysmorphic dentate nuclei (3/9). Six of those with brain abnormalities also presented with seizures.
- Nine have abnormal vision, including strabismus in four and inability to fix or follow in the two with homozygous loss-of-function variants.
- Hypotonia ranging from mild to severe was reported in 7 of the 11 individuals.
- Six have mood or behavioural disorders, particularly anxiety (3/6).
- Consistent dysmorphic facial features included microcephaly, prominent forehead, hypertelorism, down-slanting palpebral fissures, full cheeks, and micrognathia.

The severity of disease in the two siblings with homozygous disruption of ClC-3 is consistent with the drastic phenotype seen in Clcn3 KO mice. The disease was more severe in two siblings carrying homozygous loss-of-function variants with the presence of GDD, absent speech, seizures, and salt and pepper fundal pigmentation in both individuals, with one deceased at 14 months of age. The siblings also had significant neuroanatomical findings including diffusely decreased white matter volume, thin corpora callosa, small hippocampi, and disorganized cerebellar folia. Supporting biallelic inheritance for LoF variants, disruption of mouse Clcn3 results in drastic neurodegeneration with loss of the hippocampus a few months after birth and early retinal degeneration. Clcn3−/− mice display severe neurodegeneration, whereas heterozygous Clcn3+/− mice appear normal.

Patch-clamp studies were used to investigate four of the missense variants. These suggested a gain of function in two variants with increased current in HEK cells, however they also showed reduced rectification of voltage and a loss of transient current, plus decreased current amplitude, glycosylation and surface expression when expressed in oocytes, and were suspected to interfere with channel gating and a negative feedback mechanism. These effects were also shown to vary depending on pH levels. The current of the remaining two variants did not differ from WT. For heterozygous missense variants, the disruption induced may be at least partially conferred to mutant/WT homodimers and mutant/ClC-4 heterodimers.

Both loss and gain of function in this gene resulted in the same phenotype.
Sources: Literature
Mendeliome v0.8601 TNPO2 Elena Savva gene: TNPO2 was added
gene: TNPO2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TNPO2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNPO2 were set to PMID: 34314705
Phenotypes for gene: TNPO2 were set to Developmental delays, neurologic deficits and dysmorphic features
Mode of pathogenicity for gene: TNPO2 was set to Other
Review for gene: TNPO2 was set to GREEN
Added comment: PMID: 34314705 - all de novo missense variants with intellectual disability (9/9), speech impairment (15/15), motor impairment (15/15), ophthalmologic abnormalities (10/15), muscle tone abnormalities (11/15, primarily hypotonia), seizures (6/15, febrile to non-febrile), microcephaly (5/15) and MRI anomalies (7/13, 3/13 had cerebellar hypoplasia/dysplasia).

Null fly model was homozygous lethal, no obvious phenotypes in heterozygotes. Upregulated gene expression also resulted in lethality. Overexpression of some human variants in fly models resulted in "toxicity" and phenotypic defects, authors speculate two variants are GOF, 1 variant is LOF.

gnomAD: minimal PTCs present
Sources: Literature
Mendeliome v0.8601 SPTBN4 Melanie Marty Deleted their review
Mendeliome v0.8601 DNAH10 Ain Roesley gene: DNAH10 was added
gene: DNAH10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNAH10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH10 were set to 34237282
Phenotypes for gene: DNAH10 were set to primary male infertility with asthenoteratozoospermia
Penetrance for gene: DNAH10 were set to unknown
Review for gene: DNAH10 was set to GREEN
Added comment: 4x families with 5 affecteds (chets and homs - 4 missense and 2 fs). Knockout mouse models were infertile and showed significant reduction in count and motility compared to heterozygous mice
Sources: Literature
Mendeliome v0.8601 AP1G1 Zornitza Stark Marked gene: AP1G1 as ready
Mendeliome v0.8601 AP1G1 Zornitza Stark Added comment: Comment when marking as ready: Good evidence for association between mono-allelic variants and NDD, moderate evidence for bi-allelic variants causing disease.
Mendeliome v0.8601 AP1G1 Zornitza Stark Gene: ap1g1 has been classified as Green List (High Evidence).
Mendeliome v0.8601 ALDH1A2 Seb Lunke commented on gene: ALDH1A2
Mendeliome v0.8601 AP1G1 Zornitza Stark Classified gene: AP1G1 as Green List (high evidence)
Mendeliome v0.8601 AP1G1 Zornitza Stark Gene: ap1g1 has been classified as Green List (High Evidence).
Mendeliome v0.8600 SEMA3D Ain Roesley edited their review of gene: SEMA3D: Added comment: Reported as a common susceptibility loci. No reported evidence for an association with Mendelian disease. Sema3d null heterozygote and homozygote mouse model had normal intestinal innervation.; Changed publications: 28334784, 25839327; Changed phenotypes: Hirschsprung disease
Mendeliome v0.8600 AP1G1 Danielle Ariti gene: AP1G1 was added
gene: AP1G1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AP1G1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: AP1G1 were set to 34102099
Phenotypes for gene: AP1G1 were set to Neurodevelopmental disorder (NDD); Intellectual Disability; Epilepsy
Mode of pathogenicity for gene: AP1G1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: AP1G1 was set to GREEN
Added comment: Two bi-allelic homozygous missense variants were found in two distinct families with Italian and Pakistani origins; homozygous missense variants.

Eight de novo heterozygous variants were identified in nine isolated affected individuals from nine families; including five missense, two frameshift, and one intronic variant that disrupts the canonical splice acceptor site.

Knocking out AP1G1 Zebrafish model resulted in severe developmental abnormalities and increased lethality.

All individuals had neurodevelopmental disorder (NDD) including global developmental delay and ID, which varied in severity from mild to severe.
Sources: Literature
Mendeliome v0.8600 SEMA3D Zornitza Stark Marked gene: SEMA3D as ready
Mendeliome v0.8600 SEMA3D Zornitza Stark Gene: sema3d has been classified as Red List (Low Evidence).
Mendeliome v0.8600 SEMA3D Zornitza Stark Phenotypes for gene: SEMA3D were changed from to Hand and foot malformations
Mendeliome v0.8599 SEMA3D Zornitza Stark Classified gene: SEMA3D as Red List (low evidence)
Mendeliome v0.8599 SEMA3D Zornitza Stark Gene: sema3d has been classified as Red List (Low Evidence).
Mendeliome v0.8598 SPTBN1 Belinda Chong changed review comment from: PMID: 34211179
- Heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features.
- Show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics.

PMID: 33847457
- Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset.
- identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss-of-function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities).
- Identification of loss-of-function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis.
Sources: Literature; to: PMID: 34211179
- Heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures (9/29); behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features.
- Show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics.

PMID: 33847457
- Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset.
- identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss-of-function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities).
- Identification of loss-of-function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis.
Sources: Literature
Mendeliome v0.8598 SPTBN4 Zornitza Stark Marked gene: SPTBN4 as ready
Mendeliome v0.8598 SPTBN4 Zornitza Stark Gene: sptbn4 has been classified as Green List (High Evidence).
Mendeliome v0.8598 SPTBN4 Zornitza Stark Phenotypes for gene: SPTBN4 were changed from to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness (NEDHND, OMIM #617519)
Mendeliome v0.8597 TP73 Seb Lunke Classified gene: TP73 as Green List (high evidence)
Mendeliome v0.8597 TP73 Seb Lunke Gene: tp73 has been classified as Green List (High Evidence).
Mendeliome v0.8597 SPTBN4 Zornitza Stark Publications for gene: SPTBN4 were set to
Mendeliome v0.8596 SPTBN4 Zornitza Stark Mode of inheritance for gene: SPTBN4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8595 TP73 Seb Lunke Publications for gene: TP73 were set to PMID: 31130284
Mendeliome v0.8594 HMGB1 Zornitza Stark Marked gene: HMGB1 as ready
Mendeliome v0.8594 HMGB1 Zornitza Stark Gene: hmgb1 has been classified as Red List (Low Evidence).
Mendeliome v0.8594 HMGB1 Zornitza Stark Classified gene: HMGB1 as Red List (low evidence)
Mendeliome v0.8594 HMGB1 Zornitza Stark Gene: hmgb1 has been classified as Red List (Low Evidence).
Mendeliome v0.8593 SPTBN1 Zornitza Stark Marked gene: SPTBN1 as ready
Mendeliome v0.8593 SPTBN1 Zornitza Stark Gene: sptbn1 has been classified as Green List (High Evidence).
Mendeliome v0.8593 SPTBN1 Zornitza Stark Phenotypes for gene: SPTBN1 were changed from Neurodevelopmental Syndrome to Neurodevelopmental Syndrome; Intellectual disability; Seizures
Mendeliome v0.8592 EDEM3 Seb Lunke Marked gene: EDEM3 as ready
Mendeliome v0.8592 EDEM3 Seb Lunke Gene: edem3 has been classified as Green List (High Evidence).
Mendeliome v0.8592 EDEM3 Seb Lunke Phenotypes for gene: EDEM3 were changed from EDEM3-congenital disorder of glycosylation to Congenital disorder of glycosylation; Developmental delay
Mendeliome v0.8591 UBA2 Ain Roesley changed review comment from: 2x unrelated probands with isolated split hand malformation. fs variants - 1x de novo and 1x inherited from apparent unaffected mother (no radiographs of her hand available)

1x proband with unilateral split-hand malformation. Her daughter and grandson reported to have ectrofactyly but were unavailable for testing; to: 2x unrelated probands with isolated split hand malformation. fs variants - 1x de novo and 1x inherited from apparent unaffected mother (no radiographs of her hand available)

1x proband with unilateral split-hand malformation (missense). Her daughter and grandson reported to have ectrofactyly but were unavailable for testing
Mendeliome v0.8591 SPTBN1 Zornitza Stark Classified gene: SPTBN1 as Green List (high evidence)
Mendeliome v0.8591 SPTBN1 Zornitza Stark Gene: sptbn1 has been classified as Green List (High Evidence).
Mendeliome v0.8590 EDEM3 Seb Lunke Classified gene: EDEM3 as Green List (high evidence)
Mendeliome v0.8590 EDEM3 Seb Lunke Gene: edem3 has been classified as Green List (High Evidence).
Mendeliome v0.8589 UBA2 Zornitza Stark Publications for gene: UBA2 were set to PMID: 31332306; 31587267
Mendeliome v0.8588 UBA2 Zornitza Stark Classified gene: UBA2 as Green List (high evidence)
Mendeliome v0.8588 UBA2 Zornitza Stark Gene: uba2 has been classified as Green List (High Evidence).
Mendeliome v0.8587 ALDH1A2 Ain Roesley reviewed gene: ALDH1A2: Rating: RED; Mode of pathogenicity: None; Publications: 34159400; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.8587 GCNA Zornitza Stark Marked gene: GCNA as ready
Mendeliome v0.8587 GCNA Zornitza Stark Gene: gcna has been classified as Green List (High Evidence).
Mendeliome v0.8587 GCNA Zornitza Stark Classified gene: GCNA as Green List (high evidence)
Mendeliome v0.8587 GCNA Zornitza Stark Gene: gcna has been classified as Green List (High Evidence).
Mendeliome v0.8586 SEMA3D Ain Roesley gene: SEMA3D was added
gene: SEMA3D was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEMA3D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SEMA3D were set to 34159400
Penetrance for gene: SEMA3D were set to unknown
Review for gene: SEMA3D was set to RED
Added comment: 1x de novo missense in a proband with short stature, absent distal phalanges of the 5th fingers and toes, and dysplastic middle phalanges of the toes.

However, there is 4 hets in gnomAD v2
Sources: Literature
Mendeliome v0.8586 SPTBN4 Melanie Marty reviewed gene: SPTBN4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33772159; Phenotypes: Neurodevelopmental disorder with hypotonia, neuropathy, and deafness (NEDHND, OMIM #617519); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8586 TP73 Ee Ming Wong changed review comment from: - Seven individuals from five unrelated families homozygous for TP73 variants (includes 1x large deletion, 1x splice variant, 1x frameshift and 2x nonsense variants)
- Epithelial cells from TP73 variant carriers showed reduced number of ciliated cells and shortened cilia resulting in abnormal ciliary clearance of the airways compared to healthy controls; to: - Seven individuals from five unrelated families homozygous for TP73 variants (includes 1x large deletion, 1x splice variant, 1x frameshift and 2x nonsense variants)
- In vitro ciliogenesis experiments demonstrated that epithelial cells from TP73 variant carriers had reduced number of ciliated cells and shortened cilia resulting in abnormal ciliary clearance of the airways compared to healthy controls
Mendeliome v0.8586 TP73 Ee Ming Wong reviewed gene: TP73: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34077761; Phenotypes: chronic airway disease, brain malformation, lissencephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.8586 HMGB1 Ain Roesley changed review comment from: 1x de novo fs, no functional studies done but cited Itou 2011 - mouse and zebrafish studies demonstrated the role of HMGB1 in regulating digit number during embryonic limb development
Sources: Literature; to: 1x de novo fs in a proband with severe mirror image foot polydactyly. No functional studies done but cited Itou 2011 - mouse and zebrafish studies demonstrated the role of HMGB1 in regulating digit number during embryonic limb development
Sources: Literature
Mendeliome v0.8586 HMGB1 Ain Roesley gene: HMGB1 was added
gene: HMGB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HMGB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HMGB1 were set to 34159400
Phenotypes for gene: HMGB1 were set to Mirror image foot polydactyly
Penetrance for gene: HMGB1 were set to unknown
Review for gene: HMGB1 was set to RED
Added comment: 1x de novo fs, no functional studies done but cited Itou 2011 - mouse and zebrafish studies demonstrated the role of HMGB1 in regulating digit number during embryonic limb development
Sources: Literature
Mendeliome v0.8586 SPTBN1 Belinda Chong gene: SPTBN1 was added
gene: SPTBN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPTBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SPTBN1 were set to PMID: 34211179; PMID: 33847457
Phenotypes for gene: SPTBN1 were set to Neurodevelopmental Syndrome
Review for gene: SPTBN1 was set to GREEN
Added comment: PMID: 34211179
- Heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features.
- Show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics.

PMID: 33847457
- Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset.
- identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss-of-function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities).
- Identification of loss-of-function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis.
Sources: Literature
Mendeliome v0.8586 UBA2 Ain Roesley reviewed gene: UBA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34159400; Phenotypes: isolated split hand malformation; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.8586 EDEM3 Michelle Torres gene: EDEM3 was added
gene: EDEM3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EDEM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EDEM3 were set to 34143952
Phenotypes for gene: EDEM3 were set to EDEM3-congenital disorder of glycosylation
Review for gene: EDEM3 was set to GREEN
Added comment: PMID: 34143952: 7 families (11 individuals) with 6x PTV and 2x missense variants with neurodevelopmental delay and variable facial dysmorphisms. The unaffected parents were all heterozygous carriers. Functional show LoF of EDEM3 enzymatic activity.
Sources: Literature
Mendeliome v0.8586 GCNA Ain Roesley gene: GCNA was added
gene: GCNA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GCNA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GCNA were set to 33963445
Phenotypes for gene: GCNA were set to primary spermatogenic failure
Penetrance for gene: GCNA were set to unknown
Review for gene: GCNA was set to GREEN
Added comment: 7x probands all missense except 1 fs. Variants had <0.0005 MAF in gnomad v2 male cohort and absent in 5784 Dutch control cohort
no functional studies were done except for histology of Ser659Trp, revealing a Sertoli-cell only
Sources: Literature
Mendeliome v0.8586 ANK2 Zornitza Stark Marked gene: ANK2 as ready
Mendeliome v0.8586 ANK2 Zornitza Stark Gene: ank2 has been classified as Green List (High Evidence).
Mendeliome v0.8586 ANK2 Zornitza Stark Classified gene: ANK2 as Green List (high evidence)
Mendeliome v0.8586 ANK2 Zornitza Stark Gene: ank2 has been classified as Green List (High Evidence).
Mendeliome v0.8585 ANK2 Zornitza Stark gene: ANK2 was added
gene: ANK2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ANK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANK2 were set to 31983240; 22542183; 25363768; 27479843; 28554332; 30564305; 30755392; 31981491; 33004838; 33057194
Phenotypes for gene: ANK2 were set to Long QT syndrome 4, MIM# 600919; Complex neurodevelopmental disorder, MONDO:0100038
Review for gene: ANK2 was set to GREEN
Added comment: Link with cardiac abnormalities such as LongQT is DISPUTED. More than 10 unrelated individuals reported with neurodevelopmental phenotype, comprising autism/ID and de novo truncating variants, in addition to many other individuals as part of large NDD cohorts. This association has been assessed as DEFINITIVE by ClinGen.
Sources: Expert Review
Mendeliome v0.8584 PRDX3 Zornitza Stark Marked gene: PRDX3 as ready
Mendeliome v0.8584 PRDX3 Zornitza Stark Gene: prdx3 has been classified as Green List (High Evidence).
Mendeliome v0.8584 PRDX3 Zornitza Stark Classified gene: PRDX3 as Green List (high evidence)
Mendeliome v0.8584 PRDX3 Zornitza Stark Gene: prdx3 has been classified as Green List (High Evidence).
Mendeliome v0.8583 PRDX3 Hazel Phillimore changed review comment from: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex.
Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres.
The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote of a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism.
The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense.
Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity.
PRXD3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated.
Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species.
In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress.
Sources: Literature; to: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex.
Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres.
The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote with a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism.
The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense.
Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity.
PRDX3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated.
Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species.
In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress.
Sources: Literature
Mendeliome v0.8583 PRDX3 Hazel Phillimore gene: PRDX3 was added
gene: PRDX3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRDX3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDX3 were set to PMID: 33889951
Phenotypes for gene: PRDX3 were set to cerebellar ataxia (early onset, mild to moderate, progressive)
Penetrance for gene: PRDX3 were set to unknown
Review for gene: PRDX3 was set to GREEN
Added comment: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex.
Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres.
The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote of a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism.
The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense.
Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity.
PRXD3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated.
Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species.
In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress.
Sources: Literature
Mendeliome v0.8583 GSC Zornitza Stark Marked gene: GSC as ready
Mendeliome v0.8583 GSC Zornitza Stark Gene: gsc has been classified as Green List (High Evidence).
Mendeliome v0.8583 GSC Zornitza Stark Phenotypes for gene: GSC were changed from to Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities, MIM# 602471
Mendeliome v0.8582 GSC Zornitza Stark Publications for gene: GSC were set to
Mendeliome v0.8581 GSC Zornitza Stark Mode of inheritance for gene: GSC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8580 GSC Zornitza Stark reviewed gene: GSC: Rating: GREEN; Mode of pathogenicity: None; Publications: 24290375; Phenotypes: Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities, MIM# 602471; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8580 GNAI3 Zornitza Stark Marked gene: GNAI3 as ready
Mendeliome v0.8580 GNAI3 Zornitza Stark Gene: gnai3 has been classified as Green List (High Evidence).
Mendeliome v0.8580 GNAI3 Zornitza Stark Phenotypes for gene: GNAI3 were changed from to Auriculocondylar syndrome 1, OMIM #602483
Mendeliome v0.8579 GNAI3 Zornitza Stark Publications for gene: GNAI3 were set to
Mendeliome v0.8578 GNAI3 Zornitza Stark Mode of inheritance for gene: GNAI3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8577 GNAI3 Zornitza Stark reviewed gene: GNAI3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22560091; Phenotypes: Auriculocondylar syndrome 1, OMIM #602483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8577 EIF4A3 Zornitza Stark Marked gene: EIF4A3 as ready
Mendeliome v0.8577 EIF4A3 Zornitza Stark Gene: eif4a3 has been classified as Green List (High Evidence).
Mendeliome v0.8577 EIF4A3 Zornitza Stark Phenotypes for gene: EIF4A3 were changed from to Robin sequence with cleft mandible and limb anomalies, MIM# 268305; Richieri-Costa-Pereira syndrome
Mendeliome v0.8576 EIF4A3 Zornitza Stark Publications for gene: EIF4A3 were set to
Mendeliome v0.8575 EIF4A3 Zornitza Stark Mode of inheritance for gene: EIF4A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8574 EIF4A3 Zornitza Stark reviewed gene: EIF4A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24360810; Phenotypes: Robin sequence with cleft mandible and limb anomalies, MIM# 268305, Richieri-Costa-Pereira syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8574 ERBB3 Zornitza Stark edited their review of gene: ERBB3: Changed phenotypes: Lethal congenital contractural syndrome 2, MIM# 607598, Complex neurocristinopathy
Mendeliome v0.8574 ERBB3 Zornitza Stark edited their review of gene: ERBB3: Changed phenotypes: Complex neurocristinopathy
Mendeliome v0.8574 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis; Neurodevelopmental disorder with gut dysmotility to Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis; Complex neurocristinopathy
Mendeliome v0.8573 ERBB3 Zornitza Stark changed review comment from: PMID 33497358: 6 individuals from 4 unrelated families reported with severe gut dysmotility and neurodevelopmental disorder. Note variants in this gene have also recently been linked to Hirschsprung's disease.; to: PMID 33497358: 6 individuals from 4 unrelated families reported with severe gut dysmotility and other features of neurocristinopathy including short-segment HSCR, progressive axonal peripheral neuropathy, dysautonomia, hypopigmentation, deafness. Note variants in this gene have also recently been linked to Hirschsprung's disease.
Mendeliome v0.8573 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis to Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis; Neurodevelopmental disorder with gut dysmotility
Mendeliome v0.8572 ERBB3 Zornitza Stark Publications for gene: ERBB3 were set to 17701904; 31752936; 33720042
Mendeliome v0.8571 ERBB3 Zornitza Stark changed review comment from: Two families reported with contractures, positional approach used in gene discovery (2007). Another family reported more recently with a multi-system disorder but without contractures.; to: Lethal congenital contractual syndrome: Two families reported with contractures, positional approach used in gene discovery (2007). Another family reported more recently with a multi-system disorder but without contractures.
Mendeliome v0.8571 ERBB3 Zornitza Stark edited their review of gene: ERBB3: Added comment: PMID 33497358: 6 individuals from 4 unrelated families reported with severe gut dysmotility and neurodevelopmental disorder. Note variants in this gene have also recently been linked to Hirschsprung's disease.; Changed rating: GREEN; Changed publications: 17701904, 31752936, 33497358; Changed phenotypes: Lethal congenital contractural syndrome 2, MIM# 607598, Neurodevelopmental disorder with gut dysmotility
Mendeliome v0.8571 PDCL3 Zornitza Stark Marked gene: PDCL3 as ready
Mendeliome v0.8571 PDCL3 Zornitza Stark Gene: pdcl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8571 PDCL3 Zornitza Stark Classified gene: PDCL3 as Amber List (moderate evidence)
Mendeliome v0.8571 PDCL3 Zornitza Stark Gene: pdcl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8570 PDCL3 Zornitza Stark gene: PDCL3 was added
gene: PDCL3 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: PDCL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCL3 were set to 32621347
Phenotypes for gene: PDCL3 were set to Megacystis-microcolon
Review for gene: PDCL3 was set to AMBER
Added comment: Single publication (PMID 32621347): one family with two affected fetuses - one with megacystis and microcolon, and the other with megacystisis and bilateral diaphragmatic hernia (prune-belly phenotype). Compound het LOF variants in PDCL3 (one frameshift and one missense). Complete absence of PDLC3 expression demonstrated in one of the affected fetuses. No homozygous LOF PDCL3 variants in gnomAD. PCDL3 negatively modulates actin folding and is strongly expressed in smooth muscle of bladder and colon.
Sources: Expert Review
Mendeliome v0.8569 SGO1 Zornitza Stark Marked gene: SGO1 as ready
Mendeliome v0.8569 SGO1 Zornitza Stark Gene: sgo1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8569 SGO1 Zornitza Stark Phenotypes for gene: SGO1 were changed from to Chronic atrial and intestinal dysrhythmia, MIM# 616201
Mendeliome v0.8568 SGO1 Zornitza Stark Publications for gene: SGO1 were set to
Mendeliome v0.8567 SGO1 Zornitza Stark Mode of inheritance for gene: SGO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8566 SGO1 Zornitza Stark Classified gene: SGO1 as Amber List (moderate evidence)
Mendeliome v0.8566 SGO1 Zornitza Stark Gene: sgo1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8565 SGO1 Zornitza Stark reviewed gene: SGO1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25282101; Phenotypes: Chronic atrial and intestinal dysrhythmia, MIM# 616201; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8565 TYMP Zornitza Stark Marked gene: TYMP as ready
Mendeliome v0.8565 TYMP Zornitza Stark Gene: tymp has been classified as Green List (High Evidence).
Mendeliome v0.8565 TYMP Zornitza Stark Phenotypes for gene: TYMP were changed from to Mitochondrial DNA depletion syndrome 1 (MNGIE type), MIM# 603041; MNGIE: ptosis, ophthalmoplegia & ophthalmoparesis, hearing loss, neuropathy
Mendeliome v0.8564 TYMP Zornitza Stark Publications for gene: TYMP were set to
Mendeliome v0.8563 TYMP Zornitza Stark Mode of inheritance for gene: TYMP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8562 TYMP Zornitza Stark reviewed gene: TYMP: Rating: GREEN; Mode of pathogenicity: None; Publications: 9924029, 14757860; Phenotypes: Mitochondrial DNA depletion syndrome 1 (MNGIE type), MIM# 603041, MNGIE: ptosis, ophthalmoplegia & ophthalmoparesis, hearing loss, neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8562 ZNF687 Zornitza Stark Marked gene: ZNF687 as ready
Mendeliome v0.8562 ZNF687 Zornitza Stark Gene: znf687 has been classified as Green List (High Evidence).
Mendeliome v0.8562 ZNF687 Zornitza Stark Phenotypes for gene: ZNF687 were changed from to Paget disease of bone 6, MIM#616833
Mendeliome v0.8561 ZNF687 Zornitza Stark Publications for gene: ZNF687 were set to
Mendeliome v0.8560 ZNF687 Zornitza Stark Mode of inheritance for gene: ZNF687 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8559 ZNF687 Zornitza Stark Tag founder tag was added to gene: ZNF687.
Mendeliome v0.8559 ZNF687 Zornitza Stark reviewed gene: ZNF687: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Paget disease of bone 6, MIM#616833; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8559 GRHPR Zornitza Stark Marked gene: GRHPR as ready
Mendeliome v0.8559 GRHPR Zornitza Stark Gene: grhpr has been classified as Green List (High Evidence).
Mendeliome v0.8559 GRHPR Zornitza Stark Phenotypes for gene: GRHPR were changed from to Hyperoxaluria, primary, type II, MIM# 260000; MONDO:0009824
Mendeliome v0.8558 GRHPR Zornitza Stark Publications for gene: GRHPR were set to
Mendeliome v0.8557 GRHPR Zornitza Stark Mode of inheritance for gene: GRHPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8556 GRHPR Zornitza Stark reviewed gene: GRHPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 10484776, 11030416, 24116921; Phenotypes: Hyperoxaluria, primary, type II, MIM# 260000, MONDO:0009824; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8556 AGXT Zornitza Stark Marked gene: AGXT as ready
Mendeliome v0.8556 AGXT Zornitza Stark Gene: agxt has been classified as Green List (High Evidence).
Mendeliome v0.8556 AGXT Zornitza Stark Phenotypes for gene: AGXT were changed from to Hyperoxaluria, primary, type 1, MIM# 259900; MONDO:0009823
Mendeliome v0.8555 AGXT Zornitza Stark Publications for gene: AGXT were set to
Mendeliome v0.8554 AGXT Zornitza Stark Mode of inheritance for gene: AGXT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8553 AGXT Zornitza Stark reviewed gene: AGXT: Rating: GREEN; Mode of pathogenicity: None; Publications: 2039493, 19479957; Phenotypes: Hyperoxaluria, primary, type 1, MIM# 259900, MONDO:0009823; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8553 HOGA1 Zornitza Stark Marked gene: HOGA1 as ready
Mendeliome v0.8553 HOGA1 Zornitza Stark Gene: hoga1 has been classified as Green List (High Evidence).
Mendeliome v0.8553 HOGA1 Zornitza Stark Phenotypes for gene: HOGA1 were changed from to Hyperoxaluria, primary, type III MIM#613616
Mendeliome v0.8552 HOGA1 Zornitza Stark Publications for gene: HOGA1 were set to
Mendeliome v0.8551 HOGA1 Zornitza Stark Mode of inheritance for gene: HOGA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8550 ZNF687 Ain Roesley reviewed gene: ZNF687: Rating: AMBER; Mode of pathogenicity: None; Publications: 26849110, 29493781, 32106343; Phenotypes: Paget disease of bone 6, MIM#616833; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.8550 HOGA1 Paul De Fazio reviewed gene: HOGA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20797690, 21896830, 22391140; Phenotypes: Hyperoxaluria, primary, type III MIM#613616; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.8550 VPS45 Zornitza Stark Marked gene: VPS45 as ready
Mendeliome v0.8550 VPS45 Zornitza Stark Gene: vps45 has been classified as Green List (High Evidence).
Mendeliome v0.8550 VPS45 Zornitza Stark Phenotypes for gene: VPS45 were changed from to Neutropaenia, severe congenital, 5, autosomal recessive, MIM# 615285
Mendeliome v0.8549 VPS45 Zornitza Stark Publications for gene: VPS45 were set to
Mendeliome v0.8548 VPS45 Zornitza Stark Mode of inheritance for gene: VPS45 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8547 VPS45 Zornitza Stark reviewed gene: VPS45: Rating: GREEN; Mode of pathogenicity: None; Publications: 23738510, 23599270, 33623350, 32037586, 30294941; Phenotypes: Neutropaenia, severe congenital, 5, autosomal recessive, MIM# 615285; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8547 LAMTOR2 Zornitza Stark Marked gene: LAMTOR2 as ready
Mendeliome v0.8547 LAMTOR2 Zornitza Stark Gene: lamtor2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8547 LAMTOR2 Zornitza Stark Phenotypes for gene: LAMTOR2 were changed from to Immunodeficiency due to defect in MAPBP-interacting protein, MIM# 610798
Mendeliome v0.8546 LAMTOR2 Zornitza Stark Publications for gene: LAMTOR2 were set to
Mendeliome v0.8545 LAMTOR2 Zornitza Stark Mode of inheritance for gene: LAMTOR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8544 LAMTOR2 Zornitza Stark Classified gene: LAMTOR2 as Amber List (moderate evidence)
Mendeliome v0.8544 LAMTOR2 Zornitza Stark Gene: lamtor2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8543 LAMTOR2 Zornitza Stark reviewed gene: LAMTOR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 17195838, 24092934; Phenotypes: Immunodeficiency due to defect in MAPBP-interacting protein, MIM# 610798; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8543 IKZF3 Zornitza Stark Marked gene: IKZF3 as ready
Mendeliome v0.8543 IKZF3 Zornitza Stark Gene: ikzf3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8543 IKZF3 Zornitza Stark Classified gene: IKZF3 as Amber List (moderate evidence)
Mendeliome v0.8543 IKZF3 Zornitza Stark Gene: ikzf3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8542 IKZF3 Zornitza Stark gene: IKZF3 was added
gene: IKZF3 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: IKZF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKZF3 were set to 34155405
Phenotypes for gene: IKZF3 were set to Immunodeficiency 84, MIM# 619437
Review for gene: IKZF3 was set to AMBER
Added comment: Single family reported where heterozygous missense variant in this gene segregated with immunodeficiency in a mother and two children. Findings included low levels of B cells and impaired early B-cell development, variable T-cell abnormalities, hypogammaglobulinaemia, increased susceptibility to infection with Epstein-Barr virus (EBV). One individual developed lymphoma in adulthood. Mouse model recapitulated phenotype.
Sources: Expert Review
Mendeliome v0.8541 HSD17B4 Zornitza Stark Marked gene: HSD17B4 as ready
Mendeliome v0.8541 HSD17B4 Zornitza Stark Gene: hsd17b4 has been classified as Green List (High Evidence).
Mendeliome v0.8541 HSD17B4 Zornitza Stark Phenotypes for gene: HSD17B4 were changed from to D-bifunctional protein deficiency, AR (MIM#261515); Perrault syndrome 1, AR (MIM#233400)
Mendeliome v0.8540 HSD17B4 Zornitza Stark Publications for gene: HSD17B4 were set to
Mendeliome v0.8539 HSD17B4 Zornitza Stark Mode of inheritance for gene: HSD17B4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8538 HSD17B4 Zornitza Stark reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: D-bifunctional protein deficiency, AR (MIM#261515), Perrault syndrome 1, AR (MIM#233400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8538 HSD17B4 Michelle Torres reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: 27790638; Phenotypes: D-bifunctional protein deficiency, AR (MIM#261515), Perrault syndrome 1, AR (MIM#233400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8538 LCK Zornitza Stark Marked gene: LCK as ready
Mendeliome v0.8538 LCK Zornitza Stark Gene: lck has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8538 LCK Zornitza Stark Phenotypes for gene: LCK were changed from to Immunodeficiency 22 MIM# 615758; Recurrent infections; Immune dysregulation; autoimmunity; Low CD4+; low CD8+; restricted T cell repertoire; poor TCR signaling; Normal IgG/IgA; high IgM; failure to thrive; diarrhoea; lymphopaenia; hypogammaglobulinaemia; anaemia; thrombocytopaenia; CD4+ T-cell lymphopaenia
Mendeliome v0.8537 LCK Zornitza Stark Publications for gene: LCK were set to
Mendeliome v0.8536 LCK Zornitza Stark Mode of inheritance for gene: LCK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8535 LCK Zornitza Stark Classified gene: LCK as Amber List (moderate evidence)
Mendeliome v0.8535 LCK Zornitza Stark Gene: lck has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8534 LCK Zornitza Stark Classified gene: LCK as Amber List (moderate evidence)
Mendeliome v0.8534 LCK Zornitza Stark Gene: lck has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8533 LCK Zornitza Stark reviewed gene: LCK: Rating: AMBER; Mode of pathogenicity: None; Publications: 22985903, 1579166, 11021796; Phenotypes: Immunodeficiency 22 MIM# 615758, Recurrent infections, Immune dysregulation, autoimmunity, Low CD4+, low CD8+, restricted T cell repertoire, poor TCR signaling, Normal IgG/IgA, high IgM, failure to thrive, diarrhoea, lymphopenia, hypogammaglobulinemia, anaemia, thrombocytopaenia, CD4+ T-cell lymphopenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8533 DOCK8 Zornitza Stark Marked gene: DOCK8 as ready
Mendeliome v0.8533 DOCK8 Zornitza Stark Gene: dock8 has been classified as Green List (High Evidence).
Mendeliome v0.8533 DOCK8 Zornitza Stark Phenotypes for gene: DOCK8 were changed from to Hyper-IgE recurrent infection syndrome, autosomal recessive MIM# 243700; T cell Lymphopaenia; decraese T/B/NK cells; Eosinophilia; low IgM; elevated IgE; recurrent cutaneous/ viral/ bacterial/ fungal/ infections; severe atopy/allergic disease; autoimmune haemolytic anaemia; eczema; cancer diathesis
Mendeliome v0.8532 DOCK8 Zornitza Stark Publications for gene: DOCK8 were set to
Mendeliome v0.8531 DOCK8 Zornitza Stark Mode of inheritance for gene: DOCK8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8530 DOCK2 Zornitza Stark Marked gene: DOCK2 as ready
Mendeliome v0.8530 DOCK2 Zornitza Stark Gene: dock2 has been classified as Green List (High Evidence).
Mendeliome v0.8530 DOCK2 Zornitza Stark Phenotypes for gene: DOCK2 were changed from to Immunodeficiency 40 MIM# 616433; T/B-cell lymphopaenia; early-onset invasive herpes/viral/bacterial Infections; function defects in T/B/NK cells; immunodeficiency; defective IFN-mediated immunity; elevated IgM; normal IgG/IgA levels
Mendeliome v0.8529 DOCK2 Zornitza Stark Publications for gene: DOCK2 were set to
Mendeliome v0.8528 DOCK2 Zornitza Stark Mode of inheritance for gene: DOCK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8527 DOCK2 Zornitza Stark reviewed gene: DOCK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26083206, 29204803, 33928462, 30826364, 30838481, 11518968; Phenotypes: Immunodeficiency 40 MIM# 616433, T/B-cell lymphopaenia, early-onset invasive herpes/viral/bacterial Infections, function defects in T/B/NK cells, immunodeficiency, defective IFN-mediated immunity, elevated IgM, normal IgG/IgA levels; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8527 DOCK8 Danielle Ariti reviewed gene: DOCK8: Rating: GREEN; Mode of pathogenicity: None; Publications: 19776401, 20622910, 21931011, 26659092, 19898472, 25422492; Phenotypes: Hyper-IgE recurrent infection syndrome, autosomal recessive MIM# 243700, T cell Lymphopaenia, decraese T/B/NK cells, Eosinophilia, low IgM, elevated IgE, recurrent cutaneous/ viral/ bacterial/ fungal/ infections, severe atopy/allergic disease, autoimmune haemolytic anaemia, eczema, cancer diathesisc; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8527 DNMT3B Zornitza Stark Marked gene: DNMT3B as ready
Mendeliome v0.8527 DNMT3B Zornitza Stark Gene: dnmt3b has been classified as Green List (High Evidence).
Mendeliome v0.8527 DNMT3B Zornitza Stark Phenotypes for gene: DNMT3B were changed from to Immunodeficiency-centromeric instability-facial anomalies syndrome 1 MIM# 242860; facial dysmorphic features; flat nasal bridge; developmental delay; macroglossia; bacterial/opportunistic infections (recurrent); malabsorption; cytopaenia; malignancies; multiradial configurations of chromosomes 1, 9, 16; Hypogammaglobulinaemia; agammaglobulinaemia; variable antibody deficiency; decreased immunoglobulin production; low T/B/NK cells
Mendeliome v0.8526 DNMT3B Zornitza Stark Publications for gene: DNMT3B were set to
Mendeliome v0.8525 DNMT3B Zornitza Stark Mode of inheritance for gene: DNMT3B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8524 DNMT3B Zornitza Stark reviewed gene: DNMT3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20587527, 10555141, 17359920, 9718351, 10647011, 11102980, 12239717; Phenotypes: Immunodeficiency-centromeric instability-facial anomalies syndrome 1 MIM# 242860, facial dysmorphic features, flat nasal bridge, developmental delay, macroglossia, bacterial/opportunistic infections (recurrent), malabsorption, cytopaenia, malignancies, multiradial configurations of chromosomes 1, 9, 16, Hypogammaglobulinaemia, agammaglobulinaemia, variable antibody deficiency, decreased immunoglobulin production, low T/B/NK cells; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8524 TMPO Bryony Thompson Marked gene: TMPO as ready
Mendeliome v0.8524 TMPO Bryony Thompson Gene: tmpo has been classified as Red List (Low Evidence).
Mendeliome v0.8524 TMPO Bryony Thompson Classified gene: TMPO as Red List (low evidence)
Mendeliome v0.8524 TMPO Bryony Thompson Gene: tmpo has been classified as Red List (Low Evidence).
Mendeliome v0.8523 TMPO Bryony Thompson reviewed gene: TMPO: Rating: RED; Mode of pathogenicity: None; Publications: 16247757; Phenotypes: Hypertrophic cardiomyopathy, dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8523 SYNCRIP Zornitza Stark Marked gene: SYNCRIP as ready
Mendeliome v0.8523 SYNCRIP Zornitza Stark Gene: syncrip has been classified as Green List (High Evidence).
Mendeliome v0.8523 SYNCRIP Zornitza Stark Classified gene: SYNCRIP as Green List (high evidence)
Mendeliome v0.8523 SYNCRIP Zornitza Stark Gene: syncrip has been classified as Green List (High Evidence).
Mendeliome v0.8522 SYNCRIP Zornitza Stark gene: SYNCRIP was added
gene: SYNCRIP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SYNCRIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SYNCRIP were set to 34157790; 30504930; 27479843; 23020937
Phenotypes for gene: SYNCRIP were set to Global developmental delay; Intellectual disability; Autism; Myoclonic atonic seizures; Abnormality of nervous system morphology
Review for gene: SYNCRIP was set to GREEN
Added comment: Semino et al (2021 - PMID: 34157790) provide clinical details on 3 unrelated individuals with de novo SYNCRIP variants and provide a review of 5 additional subjects previously identified within large cohorts in the literature and databases.

Features included DD, ID (7/7 for whom this information was available), ASD or autistic features (4/7). MRI abnormalities were observed in 3 (widening of CSF spaces, periventricular nodular heterotopia, prominent lat. ventricles). Epilepsy (myoclonic-astatic epilepsy / Doose syndrome) was reported for 2(/8) individuals.

The 3 patients here reported were identified following trio/singleton exome with Sanger confirmation of the variants and their de novo occurrence.

Variants are in almost all cases de novo (7/7 for whom this was known) and in 5/8 cases were pLoF, in 2/8 missense SNVs while a case from DECIPHER had a 77.92 kb whole gene deletion not involving other genes with unknown inheritance.

Overall the variants reported to date include [NM_006372.5]:
1 - c.858_859del p.(Gly287Leufs*5)
2 - c.854dupA p.(Asn285Lysfs*8)
3 - c.734T>C p.(Leu245Pro)
4 - chr6:85605276-85683190 deletion (GRCh38)
5 - c.629T>C p.(Phe210Ser)
6 - c.1573_1574delinsTT p.(Gln525Leu)
7 - c.1247_1250del p.(Arg416Lysfs*145)
8 - c.1518_1519insC p.(Ala507Argfs*14)

[P1-3: this report, P4: DECIPHER 254774, P5-6: Guo et al 2019 - PMID: 30504930, P7: Lelieveld et al 2016 - PMID: 27479843, P8: Rauch et al 2012 - PMID: 23020937 / all other Refs not here reviewed, clinical details summarized by Semino et al in table 1]

SYNCRIP (also known as HNRNPQ) encodes synaptotagmin‐binding cytoplasmic RNA‐interacting protein. As the authors note, this RNA-binding protein is involved in multiple pathways associated with neuronal/muscular developmental disorders. Several references are provided for its involvement in regulation of RNA metabolism, among others sequence recognition, pre-mRNA splicing, translation, transport and degradation.

Mutations in other RNA-interacting proteins and hnRNP members (e.g. HNRNPU, HNRNPD) are associated with NDD.

The missense variant (p.Leu245Pro) is within RRM2 one of the 3 RNA recognition motif (RRM) domains of the protein. These 3 domains, corresponding to the central part of the protein (aa 150-400), are relatively intolerant to variation (based on in silico predictions and/or variation in gnomAD). Leu245 localizes within an RNA binding pocket and in silico modeling suggests alteration of the tertiary structure and RNA-binding capacity of RRM2.

There are no additional studies performed.

Overall haploinsufficiency appears to be the underlying disease mechanism based on the truncating variants and the gene deletion. [pLI in gnomAD : 1, %HI : 2.48%]

Animal models are not discussed.

There is no associated phenotype in OMIM. This gene is included in the DD panel of G2P (monoallelic LoF variants / SYNCRIP-related developmental disorder). SysID also lists SYNCRIP within the current primary ID genes.
Sources: Literature
Mendeliome v0.8521 MSN Zornitza Stark Marked gene: MSN as ready
Mendeliome v0.8521 MSN Zornitza Stark Gene: msn has been classified as Green List (High Evidence).
Mendeliome v0.8521 MSN Zornitza Stark Phenotypes for gene: MSN were changed from to Immunodeficiency 50, MIM# 300988
Mendeliome v0.8520 MSN Zornitza Stark Publications for gene: MSN were set to
Mendeliome v0.8519 MSN Zornitza Stark Mode of inheritance for gene: MSN was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8518 MSN Zornitza Stark reviewed gene: MSN: Rating: GREEN; Mode of pathogenicity: None; Publications: 27405666; Phenotypes: Immunodeficiency 50, MIM# 300988; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8518 JAGN1 Zornitza Stark Marked gene: JAGN1 as ready
Mendeliome v0.8518 JAGN1 Zornitza Stark Gene: jagn1 has been classified as Green List (High Evidence).
Mendeliome v0.8518 JAGN1 Zornitza Stark Phenotypes for gene: JAGN1 were changed from to Neutropaenia, severe congenital, 6, autosomal recessive, MIM# 616022
Mendeliome v0.8517 JAGN1 Zornitza Stark Publications for gene: JAGN1 were set to
Mendeliome v0.8516 JAGN1 Zornitza Stark Mode of inheritance for gene: JAGN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8515 JAGN1 Zornitza Stark reviewed gene: JAGN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25129144; Phenotypes: Neutropaenia, severe congenital, 6, autosomal recessive, MIM# 616022; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8515 ITGB2 Zornitza Stark Marked gene: ITGB2 as ready
Mendeliome v0.8515 ITGB2 Zornitza Stark Gene: itgb2 has been classified as Green List (High Evidence).
Mendeliome v0.8515 ITGB2 Zornitza Stark Phenotypes for gene: ITGB2 were changed from to Leukocyte adhesion deficiency, MIM# 116920
Mendeliome v0.8514 ITGB2 Zornitza Stark Publications for gene: ITGB2 were set to
Mendeliome v0.8513 ITGB2 Zornitza Stark Mode of inheritance for gene: ITGB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8512 ITGB2 Zornitza Stark reviewed gene: ITGB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 1968911, 1694220, 33957747, 32279896, 31374327; Phenotypes: Leukocyte adhesion deficiency, MIM# 116920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8512 NLRP2 Melanie Marty commented on gene: NLRP2
Mendeliome v0.8512 CAMK4 Zornitza Stark Marked gene: CAMK4 as ready
Mendeliome v0.8512 CAMK4 Zornitza Stark Gene: camk4 has been classified as Green List (High Evidence).
Mendeliome v0.8512 CAMK4 Zornitza Stark Classified gene: CAMK4 as Green List (high evidence)
Mendeliome v0.8512 CAMK4 Zornitza Stark Gene: camk4 has been classified as Green List (High Evidence).
Mendeliome v0.8511 CAMK4 Zornitza Stark gene: CAMK4 was added
gene: CAMK4 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CAMK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMK4 were set to 30262571; 33098801; 33211350
Phenotypes for gene: CAMK4 were set to Intellectual disability; Autism; Behavioral abnormality; Abnormality of movement; Dystonia; Ataxia; Chorea; Myoclonus
Review for gene: CAMK4 was set to GREEN
Added comment: 3 publications by Zech et al (2018, 2020 - PMIDs : 30262571, 33098801, 33211350) provide clinical details on 3 individuals, each harboring a private de novo CAMK4 variant.

Overlapping features included DD, ID, behavoral issues, autism and abnormal hyperkinetic movements. Dystonia and chorea in all 3 appeared 3-20 years after initial symptoms.

CAMK4 encodes Calcium/Calmodulin-dependent protein kinase IV, an important mediator of calcium-mediated activity and dynamics, particularly in the brain. It is involved in neuronal transmission, synaptic plasticity, and neuronal gene expression required for brain development and neuronal homeostasis (summary by OMIM based on Zech et al, 2018).

The 473 aa enzyme has a protein kinase domain (aa 46-300) and a C-terminal autoregulatory domain (aa 305-341) the latter comprising an autoinhibitory domain (AID / aa 305-321) and a calmodulin-binding domain (CBD / aa 322-341) [NP_001735.1 / NM_001744.4 - also used below].

Variants in all 3 subjects were identified following trio-WES and were in all cases protein-truncating, mapping to exon 10 or exon 10-intron 10 junction, expected to escape NMD and cause selective abrogation of the autoinhibitory domain (aa 305-321) leading overall to gain-of-function.

Variation databases include pLoF CAMK4 variants albeit in all cases usptream or downstream of this region (pLI of this gene in gnomAD: 0.51). Variants leading to selective abrogation of the autoregulatory domain have not been reported.

Extensive evidence for the GoF effect of the variant has been provided in the first publication. Several previous studies have demonstrated that abrogation of the AID domain leads to consitutive activation (details below).

Mouse models - though corresponding to homozygous loss of function - support a role for CAMKIV in cognitive and motor symptoms. Null mice display tremulous and ataxic movements, deficiencies in balance and sensorimotor performance associated with reduced number of Purkinje neurons (Ribar et al 2000, PMID: 11069976 - not reviewed). Wei et al (2002, PMID: 12006982 - not reviewed) provided evidence for alteration in hippocampal physiology and memory function.

Heterozygous mutations in other genes for calcium/calmodulin-dependent protein kinases (CAMKs) e.g. CAMK2A/CAMK2B (encoding subunits of CAMKII) have been reported in individuals with ID.

---

The proband in the first publication (PMID: 30262571) was a male with DD, ID, behavioral difficulties (ASD, autoaggression, stereotypies) and hyperkinetic movement disorder (myoclonus, chorea, ataxia) with severe generalized dystonia (onset at the age of 13y). Brain MRI demonstrated cerebellar atrophy.

Extensive work-up incl. karyotyping, CMA, DYT-TOR1A, THAP1, GCH1, SCA1/2/3/6/7/8/12/17, Friedreich's ataxia and FMR1 analysis was negative.F

Trio WES identified a dn splice site variant (c.981+1G>A) in the last exon-intron junction. RT-PCR followed by gel electrophoresis and Sanger in fibroblasts from an affected and control subject revealed that the proband had - as predicted by the type/location of the variant - in equal amount 2 cDNA products, a normal as well as a truncated one.

Sequencing of the shortest revealed utilization of a cryptic donor splice site upstream of the mutated donor leading to a 77bp out-of-frame deletion and introduction of a premature stop codon in the last codon (p.Lys303Serfs*28). Western blot in fibroblast cell lines revealed 2 bands corresponding to the normal protein product as well as to the p.Lys303Serfs*28 although expression of the latter was lower than that of the full length protein.

Several previous studies have shown that mutant CAMKIV species that lack the autoinhibitory domain are consitutively active (several Refs provided). Among others Chatila et al (1996, PMID: 8702940) studied an in vitro-engineered truncation mutant (Δ1-317 - truncation at position 317 of the protein) with functionally validated gain-of-function effect.

To prove enhanced activity of the splicing variant, Zech et al assessed phosphorylation of CREB (cyclic AMP-responsive element binding protein), a downstream substrate of CAMKIV. Immunobloting revealed significant increase of CREB phosphorylation in patient fibroblasts compared to controls. Overactivation of CAMKIV signaling was reversed when cells were treated with STO-609 an inhibitor of CAMKK, the ustream activator of CAMKIV.

Overall the authors demonstrated that loss of CAMKIV autoregulatory domain due to this splice variant had a gain-of-function effect.

----

Following trio-WES, Zech et al (2020 - PMID: 33098801) identified another relevant subject within cohort of 764 individuals with dystonia. This 12-y.o. male, harboring a different variant affecting the same donor site (c.981+1G>T), presented DD, ID, dystonia (onset at 3y) and additional movement disorders (myoclonus, ataxia) as well as similar behavior (ASD, autoaggression, stereotypies). [Details in suppl. p20].

----

Finally Zech et al (2020 - PMID: 33211350) reported on a 24-y.o. woman with adolescence onset choreodystonia. Other features included DD, moderate ID, absence seizures in infancy, OCD with anxiety and later diagnosis of ASD. Trio WES revealed a dn stopgain variant (c.940C>T; p.Gln314*).
Sources: Expert Review
Mendeliome v0.8510 FERMT3 Zornitza Stark Marked gene: FERMT3 as ready
Mendeliome v0.8510 FERMT3 Zornitza Stark Gene: fermt3 has been classified as Green List (High Evidence).
Mendeliome v0.8510 FERMT3 Zornitza Stark Phenotypes for gene: FERMT3 were changed from to Leukocyte adhesion deficiency, type III, MIM# 612840
Mendeliome v0.8509 FERMT3 Zornitza Stark Publications for gene: FERMT3 were set to
Mendeliome v0.8508 FERMT3 Zornitza Stark Mode of inheritance for gene: FERMT3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8507 FERMT3 Zornitza Stark reviewed gene: FERMT3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19234460, 19064721; Phenotypes: Leukocyte adhesion deficiency, type III, MIM# 612840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8507 ELANE Zornitza Stark Phenotypes for gene: ELANE were changed from Neutropaenia, severe congenital 1, autosomal dominant, MIM# 202700 to Neutropaenia, severe congenital 1, autosomal dominant, MIM# 202700; Neutropaenia, cyclic, MIM# 162800
Mendeliome v0.8506 ELANE Zornitza Stark edited their review of gene: ELANE: Changed phenotypes: Neutropaenia, severe congenital 1, autosomal dominant, MIM# 202700, Neutropaenia, cyclic, MIM# 162800
Mendeliome v0.8506 CYBB Zornitza Stark Marked gene: CYBB as ready
Mendeliome v0.8506 CYBB Zornitza Stark Gene: cybb has been classified as Green List (High Evidence).
Mendeliome v0.8506 CYBB Zornitza Stark Phenotypes for gene: CYBB were changed from to Chronic granulomatous disease, X-linked, MIM# 306400
Mendeliome v0.8505 CYBB Zornitza Stark Publications for gene: CYBB were set to
Mendeliome v0.8504 CYBB Zornitza Stark Mode of inheritance for gene: CYBB was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8503 CYBB Zornitza Stark reviewed gene: CYBB: Rating: GREEN; Mode of pathogenicity: None; Publications: 2556453, 1710153, 9585602; Phenotypes: Chronic granulomatous disease, X-linked, MIM# 306400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8503 CSF3R Zornitza Stark Marked gene: CSF3R as ready
Mendeliome v0.8503 CSF3R Zornitza Stark Gene: csf3r has been classified as Green List (High Evidence).
Mendeliome v0.8503 CSF3R Zornitza Stark Phenotypes for gene: CSF3R were changed from Neutropenia, severe congenital, 7, autosomal recessive, MIM# 617014 to Neutropaenia, severe congenital, 7, autosomal recessive, MIM# 617014
Mendeliome v0.8502 CSF3R Zornitza Stark Phenotypes for gene: CSF3R were changed from to Neutropenia, severe congenital, 7, autosomal recessive, MIM# 617014
Mendeliome v0.8501 CSF3R Zornitza Stark Publications for gene: CSF3R were set to
Mendeliome v0.8500 CSF3R Zornitza Stark Mode of inheritance for gene: CSF3R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8499 CSF3R Zornitza Stark changed review comment from: More than 5 unrelated families reported.; to: More than 5 unrelated families reported. Some reports of progression to myelodysplasia.
Mendeliome v0.8499 CSF3R Zornitza Stark reviewed gene: CSF3R: Rating: GREEN; Mode of pathogenicity: None; Publications: 24753537, 26324699, 33511998, 32966608; Phenotypes: Neutropenia, severe congenital, 7, autosomal recessive, MIM# 617014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8499 NUAK2 Zornitza Stark Phenotypes for gene: NUAK2 were changed from Anencephaly to Anencephaly 2, MIM# 619452
Mendeliome v0.8498 NUAK2 Zornitza Stark Deleted their comment
Mendeliome v0.8498 NUAK2 Zornitza Stark edited their review of gene: NUAK2: Changed phenotypes: Anencephaly 2, MIM# 619452
Mendeliome v0.8498 DBR1 Zornitza Stark Phenotypes for gene: DBR1 were changed from Viral infections of the brainstem to {Encephalitis, acute, infection (viral)-induced, susceptibility to, 11}, MIM# 619441; Viral infections of the brainstem
Mendeliome v0.8497 DBR1 Zornitza Stark edited their review of gene: DBR1: Changed phenotypes: {Encephalitis, acute, infection (viral)-induced, susceptibility to, 11}, MIM# 619441, Viral infections of the brainstem
Mendeliome v0.8497 DPYSL5 Zornitza Stark Phenotypes for gene: DPYSL5 were changed from Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities to Ritscher-Schinzel syndrome 4, MIM# 619435; Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities
Mendeliome v0.8496 DPYSL5 Zornitza Stark reviewed gene: DPYSL5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ritscher-Schinzel syndrome 4, MIM# 619435; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8496 RRP7A Zornitza Stark Phenotypes for gene: RRP7A were changed from Microcephaly to Microcephaly 28, primary, autosomal recessive MIM#619453
Mendeliome v0.8495 RRP7A Zornitza Stark edited their review of gene: RRP7A: Changed phenotypes: Microcephaly 28, primary, autosomal recessive MIM#619453
Mendeliome v0.8495 CEBPE Zornitza Stark Marked gene: CEBPE as ready
Mendeliome v0.8495 CEBPE Zornitza Stark Gene: cebpe has been classified as Green List (High Evidence).
Mendeliome v0.8495 CEBPE Zornitza Stark Phenotypes for gene: CEBPE were changed from to Specific granule deficiency, MIM# 245480
Mendeliome v0.8494 CEBPE Zornitza Stark Publications for gene: CEBPE were set to
Mendeliome v0.8493 CEBPE Zornitza Stark Mode of inheritance for gene: CEBPE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8492 CEBPE Zornitza Stark reviewed gene: CEBPE: Rating: GREEN; Mode of pathogenicity: None; Publications: 10359588, 11313242, 31256937, 29651288; Phenotypes: Specific granule deficiency, MIM# 245480; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8492 NCF1 Zornitza Stark Marked gene: NCF1 as ready
Mendeliome v0.8492 NCF1 Zornitza Stark Gene: ncf1 has been classified as Green List (High Evidence).
Mendeliome v0.8492 NCF1 Zornitza Stark Phenotypes for gene: NCF1 were changed from to Chronic granulomatous disease 1, autosomal recessive, MIM# 233700
Mendeliome v0.8491 NCF1 Zornitza Stark Publications for gene: NCF1 were set to
Mendeliome v0.8490 NCF1 Zornitza Stark Mode of inheritance for gene: NCF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8489 NCF1 Zornitza Stark reviewed gene: NCF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 2011585, 11133775, 10706888, 16972229, 16972229; Phenotypes: Chronic granulomatous disease 1, autosomal recessive, MIM# 233700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8489 COL25A1 Zornitza Stark Publications for gene: COL25A1 were set to 25500261; 26486031
Mendeliome v0.8488 COL25A1 Zornitza Stark Classified gene: COL25A1 as Green List (high evidence)
Mendeliome v0.8488 COL25A1 Zornitza Stark Gene: col25a1 has been classified as Green List (High Evidence).
Mendeliome v0.8487 COL25A1 Zornitza Stark edited their review of gene: COL25A1: Added comment: PMID: 2643702 - Patient: 273182 reported in DECIPHER, chet COL25A1 missense variants (listed as Likely Pathogenic). Phenotype includes Duane anomaly of the eye.

PMID: 31875546 - Mouse models, including Col25a1 KO and muscle-specific KO mice showed a significant reduction in the number of motor neurons in the cranial nerve nuclei, including the oculomotor, trochlear, trigeminal, and facial motor nuclei. Abnormalities in motor innervation of muscles of the head, such as the extraocular and masseter muscles, were also observed

PMID: 31875546 - Functional studies in human cell lines showed that the reported COL25A1 variants (G382R and G497X) impaired the interaction of COL25A1 with receptor protein tyrosine phosphatases, thereby reducing the ability to attract motor axons.; Changed rating: GREEN; Changed publications: 25500261, 26486031, 31875546, 26437029
Mendeliome v0.8487 LTBP1 Zornitza Stark Phenotypes for gene: LTBP1 were changed from cutis laxa syndrome to Cutis laxa, autosomal recessive, type IIE MIM#619451
Mendeliome v0.8486 STX3 Zornitza Stark Phenotypes for gene: STX3 were changed from Microvillus inclusion disease, MIM#619445 to Microvillus inclusion disease, MIM#619445; Retinal dystrophy and microvillus inclusion disease, MIM#619446
Mendeliome v0.8485 STX3 Zornitza Stark changed review comment from: At least 5 unrelated families reported.; to: At least 5 unrelated families reported.

STX3 isoform B (STX3B) predominates in the retina, so mutations in the STX3 gene that affect both isoform A (STX3A) and STX3B cause both retinal and gastrointestinal disease (RDMVID), whereas mutations in STX3 affecting only the STX3A transcript cause only diarrhoea.
Mendeliome v0.8485 STX3 Zornitza Stark edited their review of gene: STX3: Changed phenotypes: Microvillus inclusion disease, MIM#619445, Retinal dystrophy and microvillus inclusion disease, MIM#619446
Mendeliome v0.8485 STX3 Zornitza Stark Phenotypes for gene: STX3 were changed from Microvillus inclusion disease to Microvillus inclusion disease, MIM#619445
Mendeliome v0.8484 STX3 Zornitza Stark edited their review of gene: STX3: Changed phenotypes: Microvillus inclusion disease, MIM#619445
Mendeliome v0.8484 C1QA Zornitza Stark Marked gene: C1QA as ready
Mendeliome v0.8484 C1QA Zornitza Stark Gene: c1qa has been classified as Green List (High Evidence).
Mendeliome v0.8484 C1QA Zornitza Stark Phenotypes for gene: C1QA were changed from to C1q deficiency, MIM# 613652
Mendeliome v0.8483 C1QA Zornitza Stark Publications for gene: C1QA were set to
Mendeliome v0.8482 C1QA Zornitza Stark Mode of inheritance for gene: C1QA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8481 C1QA Zornitza Stark reviewed gene: C1QA: Rating: GREEN; Mode of pathogenicity: None; Publications: 9225968, 21654842, 9590289; Phenotypes: C1q deficiency, MIM# 613652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8481 CIITA Zornitza Stark Marked gene: CIITA as ready
Mendeliome v0.8481 CIITA Zornitza Stark Gene: ciita has been classified as Green List (High Evidence).
Mendeliome v0.8481 CIITA Zornitza Stark Phenotypes for gene: CIITA were changed from to Bare Lymphocyte Syndrome, type II, complementation group A MIM# 209920; varied ID; bronchiolitis; pneumonia; severe autoimmune cytopaenia; CD4 T-cell lymphopaenia; hypogammaglobulinemia; absence of antigen-induced immune response; chronic diarrhoea; recurrent respiratory infections; recurrent gastroenteritis; failure to thrive; liver/biliary tract disease
Mendeliome v0.8480 CIITA Zornitza Stark Publications for gene: CIITA were set to
Mendeliome v0.8479 CIITA Zornitza Stark Mode of inheritance for gene: CIITA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8478 CIITA Zornitza Stark reviewed gene: CIITA: Rating: GREEN; Mode of pathogenicity: None; Publications: 8402893, 9099848, 11862382, 28676232, 24789686, 20197681, 11466404, 15821736, 12910265; Phenotypes: Bare Lymphocyte Syndrome, type II, complementation group A MIM# 209920, varied ID, bronchiolitis, pneumonia, severe autoimmune cytopaenia, CD4 T-cell lymphopaenia, hypogammaglobulinemia, absence of antigen-induced immune response, chronic diarrhoea, recurrent respiratory infections, recurrent gastroenteritis, failure to thrive, liver/biliary tract disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8478 CD40LG Zornitza Stark Marked gene: CD40LG as ready
Mendeliome v0.8478 CD40LG Zornitza Stark Gene: cd40lg has been classified as Green List (High Evidence).
Mendeliome v0.8478 CD40LG Zornitza Stark Phenotypes for gene: CD40LG were changed from to Immunodeficiency, X-linked, with hyper-IgM MIM# 308230; Severe opportunistic infections (recurrent), idiopathic neutropaenia; dysgammaglobulinaemia hepatitis; cholangitis; cholangiocarcinoma; autoimmune blood cytopenias; haemolytic anaemia; thrombocytopaenia; diarrhoea; peripheral neuroectodermal tumours
Mendeliome v0.8477 CD40LG Zornitza Stark Publications for gene: CD40LG were set to
Mendeliome v0.8476 CD40LG Zornitza Stark Mode of inheritance for gene: CD40LG was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8475 CD3G Zornitza Stark Marked gene: CD3G as ready
Mendeliome v0.8475 CD3G Zornitza Stark Gene: cd3g has been classified as Green List (High Evidence).
Mendeliome v0.8475 CD3G Zornitza Stark Phenotypes for gene: CD3G were changed from to Immunodeficiency 17, CD3 gamma deficient MIM# 615607; immune deficiency; autoimmunity; failure to thrive; recurrent gastrointestinal infections; recurrent respiratory infections; autoimmune haemolytic anaemia; bronchiolitis obliterans; low CD3 complex; partial T lymphocytopenia; intractable diarrhoea.
Mendeliome v0.8474 CD3G Zornitza Stark Publications for gene: CD3G were set to
Mendeliome v0.8473 CD3G Zornitza Stark Mode of inheritance for gene: CD3G was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8472 WDR26 Zornitza Stark Marked gene: WDR26 as ready
Mendeliome v0.8472 WDR26 Zornitza Stark Gene: wdr26 has been classified as Green List (High Evidence).
Mendeliome v0.8472 WDR26 Zornitza Stark Mode of inheritance for gene: WDR26 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8471 WDR26 Zornitza Stark Publications for gene: WDR26 were set to
Mendeliome v0.8470 WDR26 Zornitza Stark Phenotypes for gene: WDR26 were changed from to Skraban-Deardorff syndrome, MIM#617616
Mendeliome v0.8469 DDB1 Zornitza Stark Phenotypes for gene: DDB1 were changed from Syndromic intellectual disability to White-Kernohan syndrome, MIM# 619426; Syndromic intellectual disability
Mendeliome v0.8468 DDB1 Zornitza Stark edited their review of gene: DDB1: Changed phenotypes: White-Kernohan syndrome, MIM# 619426, Syndromic intellectual disability
Mendeliome v0.8468 CD40LG Danielle Ariti reviewed gene: CD40LG: Rating: GREEN; Mode of pathogenicity: None; Publications: 7679801, 7679206, 8094231, 9933119, 15358621, 15997875, 7678782, 7915248, 15367912, 7518839, 16311023, 9933119, 12402041, 7882172, 33475257; Phenotypes: mmunodeficiency, X-linked, with hyper-IgM MIM# 308230, Severe opportunistic infections (recurrent), idiopathic neutropaenia, dysgammaglobulinaemia hepatitis, cholangitis, cholangiocarcinoma, autoimmune blood cytopenias, haemolytic anaemia, thrombocytopaenia, diarrhoea, peripheral neuroectodermal tumours; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8468 CD3G Danielle Ariti reviewed gene: CD3G: Rating: GREEN; Mode of pathogenicity: None; Publications: 2872416, 1635567, 17277165, 23590417, 24910257, 18482219, 31921117, 11160319; Phenotypes: Immunodeficiency 17, CD3 gamma deficient MIM# 615607, immune deficiency, autoimmunity, failure to thrive, recurrent gastrointestinal infections, recurrent respiratory infections, autoimmune haemolytic anaemia, bronchiolitis obliterans, low CD3 complex, partial T lymphocytopenia, intractable diarrhoea.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8468 WDR26 Paul De Fazio reviewed gene: WDR26: Rating: GREEN; Mode of pathogenicity: None; Publications: 28686853, 33506510, 33675273; Phenotypes: Skraban-Deardorff syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.8468 ABCD4 Zornitza Stark Publications for gene: ABCD4 were set to 22922874; 31113616; 30651581; 28572511
Mendeliome v0.8467 ABCD4 Zornitza Stark reviewed gene: ABCD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 33729671; Phenotypes: Methylmalonic aciduria and homocystinuria, cblJ type, MIM# 614857; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8467 ABCD4 Zornitza Stark Marked gene: ABCD4 as ready
Mendeliome v0.8467 ABCD4 Zornitza Stark Gene: abcd4 has been classified as Green List (High Evidence).
Mendeliome v0.8467 ABCD4 Zornitza Stark Phenotypes for gene: ABCD4 were changed from to Methylmalonic aciduria and homocystinuria, cblJ type MIM#614857
Mendeliome v0.8466 ABCD4 Zornitza Stark Publications for gene: ABCD4 were set to
Mendeliome v0.8465 ABCD4 Zornitza Stark Mode of inheritance for gene: ABCD4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8464 ABCD1 Zornitza Stark Marked gene: ABCD1 as ready
Mendeliome v0.8464 ABCD1 Zornitza Stark Gene: abcd1 has been classified as Green List (High Evidence).
Mendeliome v0.8464 ABCD1 Zornitza Stark Phenotypes for gene: ABCD1 were changed from to Adrenoleukodystrophy MIM#300100
Mendeliome v0.8463 ABCD1 Zornitza Stark Mode of inheritance for gene: ABCD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8462 ABCD1 Zornitza Stark changed review comment from: Ataxia is a feature of this progressive disorder.
Sources: Expert list; to: Well established gene-disease association.
Sources: Expert list
Mendeliome v0.8462 RAD21 Zornitza Stark Phenotypes for gene: RAD21 were changed from ?Mungan syndrome, 611376; Cornelia de Lange syndrome 4, 614701; Holoprocencephaly to Mungan syndrome, 611376; Cornelia de Lange syndrome 4, 614701; Holoprocencephaly
Mendeliome v0.8461 RAD21 Zornitza Stark Publications for gene: RAD21 were set to 31334757; 25575569; 32193685; 31704779
Mendeliome v0.8460 RAD21 Zornitza Stark reviewed gene: RAD21: Rating: GREEN; Mode of pathogenicity: None; Publications: 14638363, 32193685, 25575569; Phenotypes: Mungan syndrome, MIM# 611376: Barrett esophagus, megaduodenum, cardiac abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8460 CCBE1 Zornitza Stark Marked gene: CCBE1 as ready
Mendeliome v0.8460 CCBE1 Zornitza Stark Gene: ccbe1 has been classified as Green List (High Evidence).
Mendeliome v0.8460 CCBE1 Zornitza Stark Phenotypes for gene: CCBE1 were changed from to Hennekam lymphangiectasia- lymphoedema syndrome MIM# 235510; lymphangiectasia and lymphoedema; facial abnormalities; dysmorphic features; hypoalbuminaemia; intellectual disability; hypoglobulinaemia
Mendeliome v0.8459 CCBE1 Zornitza Stark Publications for gene: CCBE1 were set to
Mendeliome v0.8458 CCBE1 Zornitza Stark Mode of inheritance for gene: CCBE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8457 CCBE1 Zornitza Stark reviewed gene: CCBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19935664, 19911200, 19287381, 25925991, 27345729, 21778431; Phenotypes: Hennekam lymphangiectasia- lymphoedema syndrome MIM# 235510, lymphangiectasia and lymphoedema, facial abnormalities, dysmorphic features, hypoalbuminaemia, intellectual disability, hypoglobulinaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8457 CD27 Zornitza Stark Marked gene: CD27 as ready
Mendeliome v0.8457 CD27 Zornitza Stark Gene: cd27 has been classified as Green List (High Evidence).
Mendeliome v0.8457 CD27 Zornitza Stark Phenotypes for gene: CD27 were changed from to Lymphoproliferative syndrome 2; CD27-deficiency MIM# 615122; hepatosplenomegaly; reduced CD8+ T-cell function; lymphadenopathy; hepatosplenomegaly; fever; increased susceptibility to EBV infection; aplastic anaemia
Mendeliome v0.8456 CD27 Zornitza Stark Publications for gene: CD27 were set to
Mendeliome v0.8455 CD27 Zornitza Stark Mode of inheritance for gene: CD27 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8454 CD27 Zornitza Stark reviewed gene: CD27: Rating: GREEN; Mode of pathogenicity: None; Publications: 22197273, 22801960, 22365582, 25843314, 11062504; Phenotypes: Lymphoproliferative syndrome 2, CD27-deficiency MIM# 615122, hepatosplenomegaly, reduced CD8+ T-cell function, lymphadenopathy, hepatosplenomegaly, fever, increased susceptibility to EBV infection, aplastic anaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8454 ZNF148 Zornitza Stark Marked gene: ZNF148 as ready
Mendeliome v0.8454 ZNF148 Zornitza Stark Gene: znf148 has been classified as Green List (High Evidence).
Mendeliome v0.8454 ZNF148 Zornitza Stark Classified gene: ZNF148 as Green List (high evidence)
Mendeliome v0.8454 ZNF148 Zornitza Stark Gene: znf148 has been classified as Green List (High Evidence).
Mendeliome v0.8453 RAC3 Zornitza Stark Marked gene: RAC3 as ready
Mendeliome v0.8453 RAC3 Zornitza Stark Gene: rac3 has been classified as Green List (High Evidence).
Mendeliome v0.8453 RAC3 Zornitza Stark Classified gene: RAC3 as Green List (high evidence)
Mendeliome v0.8453 RAC3 Zornitza Stark Gene: rac3 has been classified as Green List (High Evidence).
Mendeliome v0.8452 PCLO Zornitza Stark Phenotypes for gene: PCLO were changed from to Pontocerebellar hypoplasia, type 3, MIM#608027
Mendeliome v0.8451 PCLO Zornitza Stark Publications for gene: PCLO were set to
Mendeliome v0.8450 PCLO Zornitza Stark Mode of inheritance for gene: PCLO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8449 ZNF148 Natalie Tan gene: ZNF148 was added
gene: ZNF148 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF148 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF148 were set to PMID: 27964749
Phenotypes for gene: ZNF148 were set to Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies; MIM#617260
Review for gene: ZNF148 was set to GREEN
Added comment: Four unrelated individuals with de novo heterozygous nonsense or frameshift mutations (all resulting in premature termination codons in the last exon of ZNF148, predicted to escape nonsense-mediated mRNA decay and result in expression of a truncated protein). Phenotype characterised by underdevelopment of the corpus callosum, mild to moderate developmental delay and ID, variable microcephaly or mild macrocephaly, short stature, feeding problems, facial dysmorphisms, and cardiac and renal malformations. No functional studies to date.
Sources: Literature
Mendeliome v0.8449 RAC3 Natalie Tan gene: RAC3 was added
gene: RAC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAC3 were set to PMID: 30293988; 29276006
Phenotypes for gene: RAC3 were set to Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, MIM#618577
Review for gene: RAC3 was set to GREEN
Added comment: Multiple unrelated individuals with heterozygous missense variants and a concordant phenotype (severe intellectual disability with brain malformations). No functional studies to date.
Sources: Literature
Mendeliome v0.8449 CHRNA4 Zornitza Stark Marked gene: CHRNA4 as ready
Mendeliome v0.8449 CHRNA4 Zornitza Stark Gene: chrna4 has been classified as Green List (High Evidence).
Mendeliome v0.8449 CHRNA4 Zornitza Stark Phenotypes for gene: CHRNA4 were changed from to Epilepsy, nocturnal frontal lobe, 1, MIM# 600513
Mendeliome v0.8448 CHRNA4 Zornitza Stark Publications for gene: CHRNA4 were set to
Mendeliome v0.8447 CHRNA4 Zornitza Stark Mode of pathogenicity for gene: CHRNA4 was changed from to Other
Mendeliome v0.8446 CHRNA4 Zornitza Stark Mode of inheritance for gene: CHRNA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8445 CHRNA4 Zornitza Stark reviewed gene: CHRNA4: Rating: GREEN; Mode of pathogenicity: Other; Publications: 14623738, 23114665; Phenotypes: Epilepsy, nocturnal frontal lobe, 1, MIM# 600513; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8445 SYP Elena Savva reviewed gene: SYP: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 23966691, 19377476; Phenotypes: Mental retardation, X-linked 96 MIM#300802; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8445 ZIC3 Zornitza Stark Marked gene: ZIC3 as ready
Mendeliome v0.8445 ZIC3 Zornitza Stark Gene: zic3 has been classified as Green List (High Evidence).
Mendeliome v0.8445 ZIC3 Zornitza Stark Phenotypes for gene: ZIC3 were changed from to Congenital heart defects, nonsyndromic, 1, X-linked (MIM#306955); Heterotaxy, visceral, 1, X-linked (MIM#306955); VACTERL association, X-linked, MIM# 314390
Mendeliome v0.8444 ZIC3 Zornitza Stark Publications for gene: ZIC3 were set to
Mendeliome v0.8443 ZIC3 Zornitza Stark Mode of inheritance for gene: ZIC3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8442 ZIC3 Zornitza Stark edited their review of gene: ZIC3: Changed phenotypes: Congenital heart defects, nonsyndromic, 1, X-linked (MIM#306955), Heterotaxy, visceral, 1, X-linked (MIM#306955), VACTERL association, X-linked, MIM# 314390
Mendeliome v0.8442 ZIC3 Zornitza Stark changed review comment from: This gene belongs on the Heterotaxy panel.; to: Well established gene-disease associations.
Mendeliome v0.8442 ZIC3 Zornitza Stark edited their review of gene: ZIC3: Changed rating: GREEN
Mendeliome v0.8442 VPS13B Zornitza Stark Marked gene: VPS13B as ready
Mendeliome v0.8442 VPS13B Zornitza Stark Gene: vps13b has been classified as Green List (High Evidence).
Mendeliome v0.8442 VPS13B Zornitza Stark Phenotypes for gene: VPS13B were changed from to Cohen syndrome, MIM# 216550
Mendeliome v0.8441 VPS13B Zornitza Stark Mode of inheritance for gene: VPS13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8440 VPS13B Zornitza Stark reviewed gene: VPS13B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cohen syndrome, MIM# 216550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8440 VPS13B Zornitza Stark Deleted their review
Mendeliome v0.8440 TULP1 Zornitza Stark Marked gene: TULP1 as ready
Mendeliome v0.8440 TULP1 Zornitza Stark Gene: tulp1 has been classified as Green List (High Evidence).
Mendeliome v0.8440 TULP1 Zornitza Stark Phenotypes for gene: TULP1 were changed from to Retinitis pigmentosa 14 M(MIM#600132); Leber congenital amaurosis 15, MIM# 613843
Mendeliome v0.8439 TULP1 Zornitza Stark Publications for gene: TULP1 were set to
Mendeliome v0.8438 TULP1 Zornitza Stark Mode of inheritance for gene: TULP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8437 TULP1 Zornitza Stark commented on gene: TULP1: Several families also reported with LCA.
Mendeliome v0.8437 TULP1 Zornitza Stark edited their review of gene: TULP1: Changed publications: 15024725
Mendeliome v0.8437 TULP1 Zornitza Stark reviewed gene: TULP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leber congenital amaurosis 15, MIM# 613843; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8437 TOPORS Zornitza Stark Marked gene: TOPORS as ready
Mendeliome v0.8437 TOPORS Zornitza Stark Gene: topors has been classified as Green List (High Evidence).
Mendeliome v0.8437 TOPORS Zornitza Stark Phenotypes for gene: TOPORS were changed from to Retinitis pigmentosa 31 (MIM#609923)
Mendeliome v0.8436 TOPORS Zornitza Stark Publications for gene: TOPORS were set to
Mendeliome v0.8435 TOPORS Zornitza Stark Mode of inheritance for gene: TOPORS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8434 SUFU Zornitza Stark Marked gene: SUFU as ready
Mendeliome v0.8434 SUFU Zornitza Stark Gene: sufu has been classified as Green List (High Evidence).
Mendeliome v0.8434 SUFU Zornitza Stark Phenotypes for gene: SUFU were changed from to Joubert syndrome 32, MIM#617757; SUFU-related neurodevelopmental syndrome; Basal cell nevus syndrome, MIM# 109400
Mendeliome v0.8433 SUFU Zornitza Stark Publications for gene: SUFU were set to
Mendeliome v0.8432 SUFU Zornitza Stark Mode of inheritance for gene: SUFU was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8431 SUFU Zornitza Stark edited their review of gene: SUFU: Changed phenotypes: Joubert syndrome 32, MIM#617757, SUFU-related neurodevelopmental syndrome, Basal cell nevus syndrome, MIM# 109400
Mendeliome v0.8431 SUFU Zornitza Stark changed review comment from: Two unrelated families described with what are postulated to be hypomorphic bi-allelic variants in this gene and Joubert syndrome. Note gene also causes dominant Basal Cell Nevus Syndrome.; to: Two unrelated families described with what are postulated to be hypomorphic bi-allelic variants in this gene and Joubert syndrome.
Mendeliome v0.8431 SUFU Zornitza Stark edited their review of gene: SUFU: Added comment: Mono-allelic variants are also associated with Basal cell nevus syndrome/predisposition to medulloblastoma.; Changed rating: GREEN; Changed publications: 28965847, 19533801, 31485359; Changed phenotypes: Joubert syndrome 32, MIM#617757, Basal cell nevus syndrome, MIM# 109400; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8431 SCNN1G Zornitza Stark Marked gene: SCNN1G as ready
Mendeliome v0.8431 SCNN1G Zornitza Stark Gene: scnn1g has been classified as Green List (High Evidence).
Mendeliome v0.8431 SCNN1G Zornitza Stark Phenotypes for gene: SCNN1G were changed from to Liddle syndrome 2, MIM# 618114; Pseudohypoaldosteronism, type I, MIM# 264350
Mendeliome v0.8430 SCNN1G Zornitza Stark Publications for gene: SCNN1G were set to
Mendeliome v0.8429 SCNN1G Zornitza Stark Mode of inheritance for gene: SCNN1G was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8428 SCNN1G Zornitza Stark Deleted their comment
Mendeliome v0.8428 SCNN1G Zornitza Stark edited their review of gene: SCNN1G: Added comment: Variants resulting in constitutive activation of epithelial sodium channel activity have been demonstrated in the beta and gamma subunits as the cause of the autosomal dominant form of hypertension, Liddle syndrome, which is characterized by volume expansion, hypokalemia, and alkalosis.

Variants causing loss of epithelial sodium channel activity cause the converse phenotype of volume depletion, hyperkalaemia and acidosis characteristic of patients with pseudohypoaldosteronism type I.

Well established gene-disease associations.; Changed rating: GREEN; Changed phenotypes: Liddle syndrome 2, MIM# 618114, Pseudohypoaldosteronism, type I, MIM# 264350; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8428 SCLT1 Zornitza Stark Marked gene: SCLT1 as ready
Mendeliome v0.8428 SCLT1 Zornitza Stark Gene: sclt1 has been classified as Green List (High Evidence).
Mendeliome v0.8428 SCLT1 Zornitza Stark Phenotypes for gene: SCLT1 were changed from to Orofaciodigital syndrome type IX; Senior-Loken syndrome; Bardet-Biedl syndrome
Mendeliome v0.8427 SCLT1 Zornitza Stark Publications for gene: SCLT1 were set to
Mendeliome v0.8426 SCLT1 Zornitza Stark Mode of inheritance for gene: SCLT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8425 RPGR Zornitza Stark Marked gene: RPGR as ready
Mendeliome v0.8425 RPGR Zornitza Stark Gene: rpgr has been classified as Green List (High Evidence).
Mendeliome v0.8425 RPGR Zornitza Stark Phenotypes for gene: RPGR were changed from to Retinitis pigmentosa 3 (MIM#300029)
Mendeliome v0.8424 RPGR Zornitza Stark Publications for gene: RPGR were set to
Mendeliome v0.8423 RPGR Zornitza Stark Mode of inheritance for gene: RPGR was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8422 PRKCSH Zornitza Stark Marked gene: PRKCSH as ready
Mendeliome v0.8422 PRKCSH Zornitza Stark Gene: prkcsh has been classified as Green List (High Evidence).
Mendeliome v0.8422 PRKCSH Zornitza Stark Phenotypes for gene: PRKCSH were changed from to Polycystic liver disease 1 (MIM#174050)
Mendeliome v0.8421 PRKCSH Zornitza Stark Publications for gene: PRKCSH were set to
Mendeliome v0.8420 PRKCSH Zornitza Stark Mode of pathogenicity for gene: PRKCSH was changed from to None
Mendeliome v0.8419 PRKCSH Zornitza Stark Mode of inheritance for gene: PRKCSH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8418 PRKCSH Zornitza Stark reviewed gene: PRKCSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 11047756, 29038287, 12529853, 12577059; Phenotypes: Polycystic liver disease 1 (MIM#174050); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8418 PRKCSH Zornitza Stark Deleted their review
Mendeliome v0.8418 POC1B Zornitza Stark Marked gene: POC1B as ready
Mendeliome v0.8418 POC1B Zornitza Stark Gene: poc1b has been classified as Green List (High Evidence).
Mendeliome v0.8418 POC1B Zornitza Stark Phenotypes for gene: POC1B were changed from to Cone-rod dystrophy 20 (MIM#615973)
Mendeliome v0.8417 POC1B Zornitza Stark Publications for gene: POC1B were set to
Mendeliome v0.8416 POC1B Zornitza Stark Mode of inheritance for gene: POC1B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8415 POC1B Zornitza Stark Deleted their review
Mendeliome v0.8415 POC1B Zornitza Stark Deleted their comment
Mendeliome v0.8415 PMM2 Zornitza Stark Marked gene: PMM2 as ready
Mendeliome v0.8415 PMM2 Zornitza Stark Gene: pmm2 has been classified as Green List (High Evidence).
Mendeliome v0.8415 PMM2 Zornitza Stark Phenotypes for gene: PMM2 were changed from to Congenital disorder of glycosylation, type Ia (MIM#212065)
Mendeliome v0.8414 PMM2 Zornitza Stark Publications for gene: PMM2 were set to
Mendeliome v0.8413 PMM2 Zornitza Stark Mode of inheritance for gene: PMM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8412 PMM2 Zornitza Stark edited their review of gene: PMM2: Added comment: Well established gene-disease association.; Changed rating: GREEN; Changed publications: 28108845
Mendeliome v0.8412 PMM2 Zornitza Stark Deleted their comment
Mendeliome v0.8412 PKHD1 Zornitza Stark Marked gene: PKHD1 as ready
Mendeliome v0.8412 PKHD1 Zornitza Stark Gene: pkhd1 has been classified as Green List (High Evidence).
Mendeliome v0.8412 PKHD1 Zornitza Stark Phenotypes for gene: PKHD1 were changed from to Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200
Mendeliome v0.8411 PKHD1 Zornitza Stark Mode of inheritance for gene: PKHD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8410 PKHD1 Zornitza Stark changed review comment from: Included due to phenotypic overlap with nephronophthisis.; to: Well established gene-disease association.
Mendeliome v0.8410 MUC1 Zornitza Stark edited their review of gene: MUC1: Changed publications: 29186029, 29156055, 29520014
Mendeliome v0.8410 MUC1 Zornitza Stark Marked gene: MUC1 as ready
Mendeliome v0.8410 MUC1 Zornitza Stark Gene: muc1 has been classified as Green List (High Evidence).
Mendeliome v0.8410 MUC1 Zornitza Stark Phenotypes for gene: MUC1 were changed from to Medullary cystic kidney disease 1 (MIM#174000)
Mendeliome v0.8409 MUC1 Zornitza Stark Publications for gene: MUC1 were set to
Mendeliome v0.8408 MUC1 Zornitza Stark Mode of inheritance for gene: MUC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8407 MUC1 Zornitza Stark Deleted their comment
Mendeliome v0.8407 MUC1 Zornitza Stark edited their review of gene: MUC1: Added comment: Well established gene-disease association, but note main variant type not readily tractable by NGS.; Changed rating: GREEN; Changed mode of pathogenicity: Other; Changed publications: Medullary cystic kidney disease 1 (MIM#174000); Changed phenotypes: Medullary cystic kidney disease 1 (MIM#174000); Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8407 KIF7 Zornitza Stark Marked gene: KIF7 as ready
Mendeliome v0.8407 KIF7 Zornitza Stark Gene: kif7 has been classified as Green List (High Evidence).
Mendeliome v0.8407 KIF7 Zornitza Stark Phenotypes for gene: KIF7 were changed from to Joubert syndrome 12, MIM# 200990; Acrocallosal syndrome, MIM# 200990; MONDO:0008708; Hydrolethalus syndrome 2, MIM# 614120
Mendeliome v0.8406 KIF7 Zornitza Stark Publications for gene: KIF7 were set to
Mendeliome v0.8405 KIF7 Zornitza Stark Mode of inheritance for gene: KIF7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8404 KIAA0753 Zornitza Stark Marked gene: KIAA0753 as ready
Mendeliome v0.8404 KIAA0753 Zornitza Stark Gene: kiaa0753 has been classified as Green List (High Evidence).
Mendeliome v0.8404 KIAA0753 Zornitza Stark Phenotypes for gene: KIAA0753 were changed from to Orofaciodigital syndrome XV, MIM# 617127; Joubert syndrome
Mendeliome v0.8403 KIAA0753 Zornitza Stark Publications for gene: KIAA0753 were set to
Mendeliome v0.8402 KIAA0753 Zornitza Stark Mode of inheritance for gene: KIAA0753 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8401 KIAA0753 Zornitza Stark edited their review of gene: KIAA0753: Changed phenotypes: Orofaciodigital syndrome XV 617127, Joubert syndrome; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8401 KIAA0753 Zornitza Stark edited their review of gene: KIAA0753: Changed rating: GREEN
Mendeliome v0.8401 KIAA0586 Zornitza Stark Marked gene: KIAA0586 as ready
Mendeliome v0.8401 KIAA0586 Zornitza Stark Gene: kiaa0586 has been classified as Green List (High Evidence).
Mendeliome v0.8401 KIAA0586 Zornitza Stark Phenotypes for gene: KIAA0586 were changed from to Joubert syndrome 23, MIM# 616490; Short-rib thoracic dysplasia 14 with polydactyly, MIM# 616546
Mendeliome v0.8400 KIAA0586 Zornitza Stark Publications for gene: KIAA0586 were set to
Mendeliome v0.8399 KIAA0586 Zornitza Stark Mode of inheritance for gene: KIAA0586 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8398 KIAA0586 Zornitza Stark edited their review of gene: KIAA0586: Changed phenotypes: Short-rib thoracic dysplasia 14 with polydactyly, MIM# 616546, Joubert syndrome
Mendeliome v0.8398 IFT52 Zornitza Stark Marked gene: IFT52 as ready
Mendeliome v0.8398 IFT52 Zornitza Stark Gene: ift52 has been classified as Green List (High Evidence).
Mendeliome v0.8398 IFT52 Zornitza Stark Phenotypes for gene: IFT52 were changed from to Short-rib thoracic dysplasia 16 with or without polydactyly, MIM# 617102
Mendeliome v0.8397 IFT52 Zornitza Stark Publications for gene: IFT52 were set to
Mendeliome v0.8396 IFT52 Zornitza Stark Mode of inheritance for gene: IFT52 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8395 IFT27 Zornitza Stark Marked gene: IFT27 as ready
Mendeliome v0.8395 IFT27 Zornitza Stark Gene: ift27 has been classified as Green List (High Evidence).
Mendeliome v0.8395 IFT27 Zornitza Stark Phenotypes for gene: IFT27 were changed from to Bardet-Biedl syndrome 19, MIM#615996
Mendeliome v0.8394 IFT27 Zornitza Stark Publications for gene: IFT27 were set to
Mendeliome v0.8393 IFT27 Zornitza Stark Mode of inheritance for gene: IFT27 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8392 POLG2 Zornitza Stark Marked gene: POLG2 as ready
Mendeliome v0.8392 POLG2 Zornitza Stark Gene: polg2 has been classified as Green List (High Evidence).
Mendeliome v0.8392 POLG2 Zornitza Stark Phenotypes for gene: POLG2 were changed from to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, MIM# 610131; Mitochondrial DNA depletion syndrome 16 , MIM# 618528
Mendeliome v0.8391 POLG2 Zornitza Stark Publications for gene: POLG2 were set to
Mendeliome v0.8390 POLG2 Zornitza Stark Mode of inheritance for gene: POLG2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8389 POLG2 Zornitza Stark reviewed gene: POLG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16685652, 21555342, 27592148, 31778857; Phenotypes: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, MIM# 610131, Mitochondrial DNA depletion syndrome 16 , MIM# 618528; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8389 PCDHGC4 Zornitza Stark Marked gene: PCDHGC4 as ready
Mendeliome v0.8389 PCDHGC4 Zornitza Stark Gene: pcdhgc4 has been classified as Green List (High Evidence).
Mendeliome v0.8389 PCDHGC4 Zornitza Stark Classified gene: PCDHGC4 as Green List (high evidence)
Mendeliome v0.8389 PCDHGC4 Zornitza Stark Gene: pcdhgc4 has been classified as Green List (High Evidence).
Mendeliome v0.8388 PCDHGC4 Zornitza Stark gene: PCDHGC4 was added
gene: PCDHGC4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PCDHGC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCDHGC4 were set to 34244665
Phenotypes for gene: PCDHGC4 were set to Intellectual disability; Seizures
Review for gene: PCDHGC4 was set to GREEN
Added comment: Eight variants reported in 19 members of nine unreleted families with a neurodevelopmental syndrome. Severe or moderate intellectual disabilty in eight families and seizures in four families. Four of the variants were LoF, in silico analysis of the remaining missense (n=3) and splice variants were predicted to be pathogenic.
Sources: Literature
Mendeliome v0.8387 ATP6V0A4 Zornitza Stark Marked gene: ATP6V0A4 as ready
Mendeliome v0.8387 ATP6V0A4 Zornitza Stark Gene: atp6v0a4 has been classified as Green List (High Evidence).
Mendeliome v0.8387 ATP6V0A4 Zornitza Stark Phenotypes for gene: ATP6V0A4 were changed from to Renal tubular acidosis, distal, autosomal recessive, MIM#602722
Mendeliome v0.8386 ATP6V0A4 Zornitza Stark Publications for gene: ATP6V0A4 were set to
Mendeliome v0.8385 ATP6V0A4 Zornitza Stark Mode of inheritance for gene: ATP6V0A4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8384 ATP6V0A4 Zornitza Stark reviewed gene: ATP6V0A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12414817, 10973252; Phenotypes: Renal tubular acidosis, distal, autosomal recessive, MIM#602722; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8384 ICK Zornitza Stark Marked gene: ICK as ready
Mendeliome v0.8384 ICK Zornitza Stark Gene: ick has been classified as Green List (High Evidence).
Mendeliome v0.8384 ICK Zornitza Stark Phenotypes for gene: ICK were changed from to Endocrine-cerebroosteodysplasia (MIM#612651)
Mendeliome v0.8383 ICK Zornitza Stark Publications for gene: ICK were set to
Mendeliome v0.8382 ICK Zornitza Stark Mode of inheritance for gene: ICK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8381 HNF1B Zornitza Stark Marked gene: HNF1B as ready
Mendeliome v0.8381 HNF1B Zornitza Stark Gene: hnf1b has been classified as Green List (High Evidence).
Mendeliome v0.8381 HNF1B Zornitza Stark Tag SV/CNV tag was added to gene: HNF1B.
Mendeliome v0.8381 HNF1B Zornitza Stark Phenotypes for gene: HNF1B were changed from to Renal cysts and diabetes syndrome, MIM# 137920
Mendeliome v0.8380 HNF1B Zornitza Stark Mode of inheritance for gene: HNF1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8379 HNF1B Zornitza Stark changed review comment from: Included due to phenotypic overlap with nephronophthisis.; to: Well established gene-disease association, CNVs common.
Mendeliome v0.8379 GDF1 Zornitza Stark Marked gene: GDF1 as ready
Mendeliome v0.8379 GDF1 Zornitza Stark Gene: gdf1 has been classified as Green List (High Evidence).
Mendeliome v0.8379 GDF1 Zornitza Stark Phenotypes for gene: GDF1 were changed from to Congenital heart defects, multiple types, 6 613854; Right atrial isomerism (Ivemark) 208530
Mendeliome v0.8378 GDF1 Zornitza Stark Publications for gene: GDF1 were set to
Mendeliome v0.8377 GDF1 Zornitza Stark Mode of inheritance for gene: GDF1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.8376 GDF1 Zornitza Stark edited their review of gene: GDF1: Added comment: PMID: 32144877 - founder PTC in Arab population causing congenital heart detects AND right isomerism in 3 (unrelated?) families. Reviews other publications and reports additional chet (two PTC) or homozygous (missense) families with situs inversus and/or heart defects. No apparent genotype-phenotype correlation btw dominant and recessive disease.; Changed rating: GREEN; Changed publications: 32144877; Changed phenotypes: Congenital heart defects, multiple types, 6 613854, Right atrial isomerism (Ivemark) 208530; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8376 EVC2 Zornitza Stark Marked gene: EVC2 as ready
Mendeliome v0.8376 EVC2 Zornitza Stark Gene: evc2 has been classified as Green List (High Evidence).
Mendeliome v0.8376 EVC2 Zornitza Stark Phenotypes for gene: EVC2 were changed from to Ellis-van Creveld syndrome (MIM#225500)
Mendeliome v0.8375 EVC2 Zornitza Stark Publications for gene: EVC2 were set to
Mendeliome v0.8374 EVC2 Zornitza Stark Mode of inheritance for gene: EVC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8373 EVC Zornitza Stark Marked gene: EVC as ready
Mendeliome v0.8373 EVC Zornitza Stark Gene: evc has been classified as Green List (High Evidence).
Mendeliome v0.8373 EVC Zornitza Stark Phenotypes for gene: EVC were changed from to Ellis-van Creveld syndrome, MIM# 225500
Mendeliome v0.8372 EVC Zornitza Stark Publications for gene: EVC were set to
Mendeliome v0.8371 EVC Zornitza Stark Mode of inheritance for gene: EVC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8370 DCDC2 Zornitza Stark Marked gene: DCDC2 as ready
Mendeliome v0.8370 DCDC2 Zornitza Stark Gene: dcdc2 has been classified as Green List (High Evidence).
Mendeliome v0.8370 DCDC2 Zornitza Stark Phenotypes for gene: DCDC2 were changed from to Nephronophthisis 19, MIM# 616217; Sclerosing cholangitis, neonatal, MIM# 617394
Mendeliome v0.8369 DCDC2 Zornitza Stark Publications for gene: DCDC2 were set to
Mendeliome v0.8368 DCDC2 Zornitza Stark Mode of inheritance for gene: DCDC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8367 DCDC2 Zornitza Stark changed review comment from: Only a single case with nephronophthisis, most reports are for cholangitis, though zebrafish model has renal cysts.; to: At least 5 families reported with cholangitis, and two with nephronophthisis, though zebrafish model has renal cysts.
Mendeliome v0.8367 DCDC2 Zornitza Stark edited their review of gene: DCDC2: Changed rating: GREEN; Changed publications: 25557784, 27319779, 27469900; Changed phenotypes: Nephronophthisis 19, MIM# 616217, Sclerosing cholangitis, neonatal, MIM# 617394; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8367 CRELD1 Zornitza Stark Marked gene: CRELD1 as ready
Mendeliome v0.8367 CRELD1 Zornitza Stark Gene: creld1 has been classified as Green List (High Evidence).
Mendeliome v0.8367 CRELD1 Zornitza Stark Phenotypes for gene: CRELD1 were changed from to Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217
Mendeliome v0.8366 CRELD1 Zornitza Stark Publications for gene: CRELD1 were set to
Mendeliome v0.8365 CRELD1 Zornitza Stark Mode of inheritance for gene: CRELD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8364 CRELD1 Zornitza Stark reviewed gene: CRELD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22740159; Phenotypes: Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8364 CRB2 Zornitza Stark Marked gene: CRB2 as ready
Mendeliome v0.8364 CRB2 Zornitza Stark Gene: crb2 has been classified as Green List (High Evidence).
Mendeliome v0.8364 CRB2 Zornitza Stark Phenotypes for gene: CRB2 were changed from to Ventriculomegaly with cystic kidney disease, MIM# 219730; Focal segmental glomerulosclerosis 9, MIM# 616220
Mendeliome v0.8363 CRB2 Zornitza Stark Publications for gene: CRB2 were set to
Mendeliome v0.8362 CRB2 Zornitza Stark Mode of inheritance for gene: CRB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8361 CRB2 Zornitza Stark changed review comment from: More than 7 unrelated families reported, mouse model. Some have presented predominantly with proteinuria, and some more with a multi-system ciliopathy phenotype, and yet others with RP.; to: VM with renal disease: More than 7 unrelated families reported, mouse model. Some have presented predominantly with proteinuria, and some more with a multi-system ciliopathy phenotype, and yet others with RP.

FSGS: at least 4 families and animal model.
Mendeliome v0.8361 CRB2 Zornitza Stark edited their review of gene: CRB2: Changed publications: 25557780, 33687977, 32051522, 30212996, 33575434, 31438467, 30593785, 25557779; Changed phenotypes: Ventriculomegaly with cystic kidney disease, MIM# 219730, Focal segmental glomerulosclerosis 9, MIM# 616220
Mendeliome v0.8361 CEP55 Zornitza Stark Marked gene: CEP55 as ready
Mendeliome v0.8361 CEP55 Zornitza Stark Gene: cep55 has been classified as Green List (High Evidence).
Mendeliome v0.8361 CEP55 Zornitza Stark Phenotypes for gene: CEP55 were changed from to Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM# 236500
Mendeliome v0.8360 CEP55 Zornitza Stark Publications for gene: CEP55 were set to
Mendeliome v0.8359 CEP55 Zornitza Stark Mode of inheritance for gene: CEP55 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8358 CEP55 Zornitza Stark reviewed gene: CEP55: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM# 236500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8358 CENPF Zornitza Stark Marked gene: CENPF as ready
Mendeliome v0.8358 CENPF Zornitza Stark Gene: cenpf has been classified as Green List (High Evidence).
Mendeliome v0.8358 CENPF Zornitza Stark Phenotypes for gene: CENPF were changed from to Stromme syndrome (MIM#243605)
Mendeliome v0.8357 CENPF Zornitza Stark Publications for gene: CENPF were set to
Mendeliome v0.8356 CENPF Zornitza Stark Mode of inheritance for gene: CENPF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8355 C8orf37 Zornitza Stark Marked gene: C8orf37 as ready
Mendeliome v0.8355 C8orf37 Zornitza Stark Gene: c8orf37 has been classified as Green List (High Evidence).
Mendeliome v0.8355 C8orf37 Zornitza Stark Phenotypes for gene: C8orf37 were changed from to Bardet-Biedl syndrome 21, MIM#617406; Retinitis pigmentosa 64, MIM#614500
Mendeliome v0.8354 C8orf37 Zornitza Stark Publications for gene: C8orf37 were set to
Mendeliome v0.8353 C8orf37 Zornitza Stark Mode of inheritance for gene: C8orf37 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8352 C2CD3 Zornitza Stark Marked gene: C2CD3 as ready
Mendeliome v0.8352 C2CD3 Zornitza Stark Gene: c2cd3 has been classified as Green List (High Evidence).
Mendeliome v0.8352 C2CD3 Zornitza Stark Phenotypes for gene: C2CD3 were changed from to Orofaciodigital syndrome XIV, MIM# 615948; MONDO:0014413
Mendeliome v0.8351 C2CD3 Zornitza Stark Publications for gene: C2CD3 were set to
Mendeliome v0.8350 C2CD3 Zornitza Stark Mode of inheritance for gene: C2CD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8348 CHRM3 Zornitza Stark Marked gene: CHRM3 as ready
Mendeliome v0.8348 CHRM3 Zornitza Stark Gene: chrm3 has been classified as Green List (High Evidence).
Mendeliome v0.8348 CHRM3 Zornitza Stark Phenotypes for gene: CHRM3 were changed from to Prune belly syndrome, MIM# 100100
Mendeliome v0.8347 CHRM3 Zornitza Stark Publications for gene: CHRM3 were set to
Mendeliome v0.8346 CHRM3 Zornitza Stark Mode of inheritance for gene: CHRM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8345 CHRM3 Zornitza Stark reviewed gene: CHRM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22077972, 31441039; Phenotypes: Prune belly syndrome, MIM# 100100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8345 ARHGAP42 Zornitza Stark Marked gene: ARHGAP42 as ready
Mendeliome v0.8345 ARHGAP42 Zornitza Stark Gene: arhgap42 has been classified as Red List (Low Evidence).
Mendeliome v0.8345 ARHGAP42 Zornitza Stark gene: ARHGAP42 was added
gene: ARHGAP42 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARHGAP42 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARHGAP42 were set to 34232960
Phenotypes for gene: ARHGAP42 were set to Interstitial lung disease; systemic hypertension; immunological abnormalities
Review for gene: ARHGAP42 was set to RED
Added comment: Single individual reported with homozygous LoF variant, chILD disorder, systemic hypertension, and immunological findings.
Sources: Literature
Mendeliome v0.8344 KIAA0556 Zornitza Stark changed review comment from: 5 individuals from two families reported, supportive mouse model.; to: 5 individuals from two families reported, supportive mouse model.

New HGNC approved name is KATNIP.
Mendeliome v0.8344 KIAA0556 Zornitza Stark Tag new gene name tag was added to gene: KIAA0556.
Mendeliome v0.8344 KIAA0556 Zornitza Stark Marked gene: KIAA0556 as ready
Mendeliome v0.8344 KIAA0556 Zornitza Stark Gene: kiaa0556 has been classified as Green List (High Evidence).
Mendeliome v0.8344 KIAA0556 Zornitza Stark Phenotypes for gene: KIAA0556 were changed from to Joubert syndrome 26, MIM# 616784
Mendeliome v0.8343 KIAA0556 Zornitza Stark Publications for gene: KIAA0556 were set to
Mendeliome v0.8342 KIAA0556 Zornitza Stark Mode of inheritance for gene: KIAA0556 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8341 KIAA0556 Zornitza Stark reviewed gene: KIAA0556: Rating: GREEN; Mode of pathogenicity: None; Publications: 26714646, 27245168; Phenotypes: Joubert syndrome 26, MIM# 616784; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8341 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; Retinitis pigmentosa 80, MIM# 617781 to Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964; Retinitis pigmentosa 80, MIM# 617781
Mendeliome v0.8340 IFT122 Zornitza Stark Phenotypes for gene: IFT122 were changed from Cranioectodermal dysplasia 1, MIM# MIM#218330 to Cranioectodermal dysplasia 1, MIM# MIM#218330; MONDO:0021093
Mendeliome v0.8339 LINGO4 Zornitza Stark Marked gene: LINGO4 as ready
Mendeliome v0.8339 LINGO4 Zornitza Stark Gene: lingo4 has been classified as Green List (High Evidence).
Mendeliome v0.8339 LINGO4 Zornitza Stark Classified gene: LINGO4 as Green List (high evidence)
Mendeliome v0.8339 LINGO4 Zornitza Stark Gene: lingo4 has been classified as Green List (High Evidence).
Mendeliome v0.8338 ARFGEF3 Zornitza Stark Marked gene: ARFGEF3 as ready
Mendeliome v0.8338 ARFGEF3 Zornitza Stark Gene: arfgef3 has been classified as Green List (High Evidence).
Mendeliome v0.8338 ARFGEF3 Zornitza Stark Classified gene: ARFGEF3 as Green List (high evidence)
Mendeliome v0.8338 ARFGEF3 Zornitza Stark Gene: arfgef3 has been classified as Green List (High Evidence).
Mendeliome v0.8337 IMPDH2 Zornitza Stark Marked gene: IMPDH2 as ready
Mendeliome v0.8337 IMPDH2 Zornitza Stark Gene: impdh2 has been classified as Green List (High Evidence).
Mendeliome v0.8337 IMPDH2 Zornitza Stark Phenotypes for gene: IMPDH2 were changed from Dystonia to Neurodevelopmental disorder with dystonia
Mendeliome v0.8336 IMPDH2 Zornitza Stark Classified gene: IMPDH2 as Green List (high evidence)
Mendeliome v0.8336 IMPDH2 Zornitza Stark Gene: impdh2 has been classified as Green List (High Evidence).
Mendeliome v0.8335 LINGO4 Laura Raiti gene: LINGO4 was added
gene: LINGO4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LINGO4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LINGO4 were set to PMID: 33098801
Phenotypes for gene: LINGO4 were set to Developmental Delay, Intellectual disability, speech disorder
Review for gene: LINGO4 was set to GREEN
Added comment: 3 unrelated individuals
1 x individual compound heterozygous for 2x missense variants:
c.679C>A; c.1262G>A p.Leu227Met; p.Arg421Gln comp het. Phenotype: infancy-onset
generalized dystonia; DD/hypo, ID, speech disorder (isolated plus non-MD symptoms) NDD

1 x individual homozygous for missense variant: c.679C>A p.Leu227Met Phenotype: DD/hypo, ID, speech disorder

1 x individual homozygous for missense variant: c.1673G>A p.Ser558Asn Phenotype: DD/hypo, ID, speech disorder
Sources: Literature
Mendeliome v0.8335 ARFGEF3 Laura Raiti gene: ARFGEF3 was added
gene: ARFGEF3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARFGEF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARFGEF3 were set to PMID: 33098801
Phenotypes for gene: ARFGEF3 were set to Dystonia
Review for gene: ARFGEF3 was set to GREEN
Added comment: 3 x unrelated individuals
1 x de novo missense variant: c.6212T>C p.Met2071Thr, phenotype: infancy-onset generalized dystonia (isolated)
1x stop-gain variant c.1773T>G p.Tyr591* (inherited from mosaic mother), phenotype: infancy-onset generalized dystonia (isolated)
1 x de novo missense variant (Gene Matcher) c.250A>C p.Met84Leu childhood-onset generalized dystonia (isolated)
Sources: Literature
Mendeliome v0.8335 IMPDH2 Laura Raiti gene: IMPDH2 was added
gene: IMPDH2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IMPDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IMPDH2 were set to PMID: 33098801
Phenotypes for gene: IMPDH2 were set to Dystonia
Review for gene: IMPDH2 was set to GREEN
Added comment: 6 unrelated individuals
1x individual in a dystonia cohort index case with infancy-onset dystonia and other neurological manifestations with a de-novo missense variant, c.338G>A (p.Gly113Glu) in IMPDH2, predicted to disrupt an invariant residue within the cystathionine-β-synthase (CBS) domain pair of the encoded protein.
IMPDH2 encodes IMPDH2, a key enzyme in the purine biosynthetic pathway, expressed throughout the brain and not linked previously to any human Mendelian condition.
1x individual with a de-novo substitution, c.337G>A (p.Gly113Arg), was found in in-house whole-exome sequencing data from 500 individuals with neurodevelopmental disorders. Through GeneMatcher, de novo variants identified:
3 x missense: c.729G>C (p.Gln243His), c.619G>C (p.Gly207Arg), and c.619G>A (p.Gly207Arg)
1 x deletion: c.478_480delTCC (p.Ser160del)
The six variants were predicted to be deleterious and none of them seen in control databases. All affected conserved amino acids and resided in and around the cystathionine-β-synthase domain pair.
The described variants are situated in and around the CBS domain pair, a regulatory element in which clustering of pathogenic missense variants has already been shown for the homologue of IMPDH2, IMPDH1.

The variant carriers shared similar neurodevelopmental phenotypes. Apart from the dystonia cohort index case, one participant had evidence of dystonic posturing. Modelling of the variants on 3D protein structures revealed spatial clustering near specific functional sites, predicted to result in deregulation of IMPDH2 activity. Additionally, thermal-shift assays showed that the c.619G>A (p.Gly207Arg) variant, identified as within the CBS domain pair, and c.729G>C (p.Gln243His), which is in close vicinity, affected the stability or folding behaviour of IMPDH2.
Sources: Literature
Mendeliome v0.8335 DYNC2H1 Zornitza Stark Publications for gene: DYNC2H1 were set to 19442771; 19361615; 22499340; 23456818; 27925158
Mendeliome v0.8334 DYNC2H1 Zornitza Stark changed review comment from: More than 50 unrelated families reported.; to: More than 50 unrelated families reported with predominantly skeletal dysplasia.

Association with RP: - Five affected probands with homozygous and compound heterozygous missense and PTC variants - Associated with the NM_001080463.1 transcript (predominant isoform in retina from retinal organoid studies). PMID 32753734
Mendeliome v0.8334 DYNC2H1 Zornitza Stark edited their review of gene: DYNC2H1: Changed publications: 19442771, 19361615, 22499340, 23456818, 27925158, 32753734; Changed phenotypes: Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091, MONDO:0013127, Non-syndromic retinitis pigmentosa
Mendeliome v0.8334 STK36 Zornitza Stark Phenotypes for gene: STK36 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 46, MIM# 619436
Mendeliome v0.8333 STK36 Zornitza Stark edited their review of gene: STK36: Changed phenotypes: Ciliary dyskinesia, primary, 46, MIM# 619436
Mendeliome v0.8333 KIF20A Zornitza Stark Marked gene: KIF20A as ready
Mendeliome v0.8333 KIF20A Zornitza Stark Gene: kif20a has been classified as Red List (Low Evidence).
Mendeliome v0.8333 KIF20A Zornitza Stark edited their review of gene: KIF20A: Changed rating: RED
Mendeliome v0.8333 KIF20A Zornitza Stark gene: KIF20A was added
gene: KIF20A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF20A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF20A were set to 29357359
Phenotypes for gene: KIF20A were set to Cardiomyopathy, familial restrictive, 6, MIM# 619433
Review for gene: KIF20A was set to GREEN
Added comment: Single family reported, two affected sibs, perinatal lethal cardiomyopathy, compound het variants in this gene.
Sources: Literature
Mendeliome v0.8332 ACTG2 Zornitza Stark Phenotypes for gene: ACTG2 were changed from Visceral myopathy, MIM#155310 to Visceral myopathy, MIM#155310; Megacystis-microcolon-intestinal hypoperistalsis syndrome 5, MIM# 619431
Mendeliome v0.8331 ACTG2 Zornitza Stark edited their review of gene: ACTG2: Changed phenotypes: Visceral myopathy, MIM#155310, Megacystis-microcolon-intestinal hypoperistalsis syndrome 5, MIM# 619431
Mendeliome v0.8331 B2M Zornitza Stark Marked gene: B2M as ready
Mendeliome v0.8331 B2M Zornitza Stark Gene: b2m has been classified as Green List (High Evidence).
Mendeliome v0.8331 B2M Zornitza Stark Phenotypes for gene: B2M were changed from to Immunodeficiency 43 MIM# 241600; Sinopulmonary infections; Purple-red skin lesions; Decreased serum IgG; Decreased B cells; Absent β2m associated proteins MHC-I, CD1a, CD1b, and CD1c; MONDO:0009434; Amyloidosis, familial visceral, MIM# 105200
Mendeliome v0.8330 B2M Zornitza Stark Publications for gene: B2M were set to
Mendeliome v0.8329 B2M Zornitza Stark Mode of inheritance for gene: B2M was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8328 B2M Zornitza Stark reviewed gene: B2M: Rating: GREEN; Mode of pathogenicity: None; Publications: 4186801, 16549777, 25702838, 11118151, 6165007, 22693999; Phenotypes: Immunodeficiency 43 MIM# 241600, Sinopulmonary infections, Purple-red skin lesions, Decreased serum IgG, Decreased B cells, Absent β2m associated proteins MHC-I, CD1a, CD1b, and CD1c, MONDO:0009434, Amyloidosis, familial visceral, MIM# 105200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8328 AK2 Zornitza Stark Phenotypes for gene: AK2 were changed from Reticular dysgenesis, MIM# 267500 to Reticular dysgenesis, MIM# 267500; MONDO:0009973
Mendeliome v0.8327 AK2 Zornitza Stark Publications for gene: AK2 were set to 19043416
Mendeliome v0.8326 AK2 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association.

PMID: 19043417 (2009). 6 affected individuals from 5 unrelated families (3 of the families showed evidence of consanguinity). Homozygous (5 individuals) and compound heterozygous (1 individual) variants in the AK2 gene. Variants included missense, deletion and inframe indel, resulting in protein LoF. Available parents were sequenced and found heterozygous for the variants, supporting bi-allelic inheritance.

PMID: 19043416 (2009). 7 affected individuals from 6 unrelated families (2 separate consanguineous & 4 non-consanguineous families). Homozygous and compound heterozygous variants detected (missense, deletion, inframe indel), resulting in protein LoF. Reticular dysgenesis phenotype including Leukopenia, lymphopenia and agranulocytosis in all affected individuals and sensorineural deafness in 7 individuals.
Mendeliome v0.8326 AK2 Zornitza Stark edited their review of gene: AK2: Changed phenotypes: Reticular dysgenesis, MIM# 267500, MONDO:0009973
Mendeliome v0.8326 AK2 Zornitza Stark edited their review of gene: AK2: Changed publications: 19043416, 19043417
Mendeliome v0.8326 TMEM126A Zornitza Stark Marked gene: TMEM126A as ready
Mendeliome v0.8326 TMEM126A Zornitza Stark Gene: tmem126a has been classified as Green List (High Evidence).
Mendeliome v0.8326 TMEM126A Zornitza Stark Phenotypes for gene: TMEM126A were changed from to Optic atrophy 7, MIM# 612989; MONDO:0013069; Syndromic auditory neuropathy spectrum disorder
Mendeliome v0.8325 TMEM126A Zornitza Stark Publications for gene: TMEM126A were set to
Mendeliome v0.8324 TMEM126A Zornitza Stark Mode of inheritance for gene: TMEM126A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8323 TMEM126A Zornitza Stark reviewed gene: TMEM126A: Rating: GREEN; Mode of pathogenicity: None; Publications: 19327736, 20405026, 22815638, 33879611, 31119195, 30961538; Phenotypes: Optic atrophy 7, MIM# 612989, MONDO:0013069, Syndromic auditory neuropathy spectrum disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8323 MYC Zornitza Stark Marked gene: MYC as ready
Mendeliome v0.8323 MYC Zornitza Stark Gene: myc has been classified as Red List (Low Evidence).
Mendeliome v0.8323 MYC Zornitza Stark Phenotypes for gene: MYC were changed from to Burkitt lymphoma, somatic, MIM# 113970
Mendeliome v0.8322 MYC Zornitza Stark Mode of inheritance for gene: MYC was changed from Unknown to Other
Mendeliome v0.8321 MYC Zornitza Stark Classified gene: MYC as Red List (low evidence)
Mendeliome v0.8321 MYC Zornitza Stark Gene: myc has been classified as Red List (Low Evidence).
Mendeliome v0.8320 MYC Zornitza Stark reviewed gene: MYC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Burkitt lymphoma, somatic, MIM# 113970; Mode of inheritance: Other
Mendeliome v0.8318 ATG7 Zornitza Stark changed review comment from: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature; to: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The more severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature
Mendeliome v0.8318 ATG7 Zornitza Stark changed review comment from: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.
Sources: Literature; to: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature
Mendeliome v0.8318 ATG7 Zornitza Stark Marked gene: ATG7 as ready
Mendeliome v0.8318 ATG7 Zornitza Stark Gene: atg7 has been classified as Green List (High Evidence).
Mendeliome v0.8318 ATG7 Zornitza Stark Classified gene: ATG7 as Green List (high evidence)
Mendeliome v0.8318 ATG7 Zornitza Stark Gene: atg7 has been classified as Green List (High Evidence).
Mendeliome v0.8317 ATG7 Zornitza Stark gene: ATG7 was added
gene: ATG7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG7 were set to 34161705
Phenotypes for gene: ATG7 were set to Spinocerebellar ataxia, SCAR31, MIM#619422
Review for gene: ATG7 was set to GREEN
Added comment: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.
Sources: Literature
Mendeliome v0.8316 ADA Zornitza Stark Marked gene: ADA as ready
Mendeliome v0.8316 ADA Zornitza Stark Gene: ada has been classified as Green List (High Evidence).
Mendeliome v0.8316 ADA Zornitza Stark Phenotypes for gene: ADA were changed from to Severe combined immunodeficiency due to ADA deficiency, MIM# 102700; MONDO:0007064
Mendeliome v0.8315 ADA Zornitza Stark Publications for gene: ADA were set to
Mendeliome v0.8314 ADA Zornitza Stark Mode of inheritance for gene: ADA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8313 ADA Zornitza Stark reviewed gene: ADA: Rating: GREEN; Mode of pathogenicity: None; Publications: 3007108, 3475710, 8178821, 8227344, 2783588; Phenotypes: Severe combined immunodeficiency due to ADA deficiency, MIM# 102700, MONDO:0007064; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8313 C2orf69 Zornitza Stark Marked gene: C2orf69 as ready
Mendeliome v0.8313 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Mendeliome v0.8313 C2orf69 Zornitza Stark Classified gene: C2orf69 as Green List (high evidence)
Mendeliome v0.8313 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Mendeliome v0.8312 C2orf69 Zornitza Stark gene: C2orf69 was added
gene: C2orf69 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2orf69 were set to 34038740; 33945503
Phenotypes for gene: C2orf69 were set to Combined oxidative phosphorylation deficiency-53 (COXPD53), MIM#619423
Review for gene: C2orf69 was set to GREEN
Added comment: PMID 34038740: 20 affected children from 8 unrelated families reported, presenting with fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. Endogenous C2ORF69 was found to be (1) loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. Zebrafish model.

PMID 33945503: 8 individuals from 5 families reported with muscle hypotonia, developmental delay, progressive microcephaly, and brain MRI abnormalities. Age at onset ranged from birth to 6 months of age. Six patients had vision impairment, liver abnormalities, inflammation/inflammatory arthritis, and 5 patients had seizures.
Sources: Literature
Mendeliome v0.8311 KDM3B Zornitza Stark Phenotypes for gene: KDM3B were changed from Intellectual disability; dysmorphic features; short stature to Diets-Jongmans syndrome, MIM# 618846; Intellectual disability; dysmorphic features; short stature
Mendeliome v0.8310 KDM3B Zornitza Stark edited their review of gene: KDM3B: Changed phenotypes: Diets-Jongmans syndrome, MIM# 618846, Intellectual disability, dysmorphic features, short stature
Mendeliome v0.8310 NYNRIN Zornitza Stark Marked gene: NYNRIN as ready
Mendeliome v0.8310 NYNRIN Zornitza Stark Gene: nynrin has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8310 NYNRIN Zornitza Stark Phenotypes for gene: NYNRIN were changed from to Wilms tumour predisposition
Mendeliome v0.8309 NYNRIN Zornitza Stark Classified gene: NYNRIN as Amber List (moderate evidence)
Mendeliome v0.8309 NYNRIN Zornitza Stark Gene: nynrin has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8308 FBXW7 Zornitza Stark Phenotypes for gene: FBXW7 were changed from FBXW7-related neurodevelopmental syndrome to FBXW7-related neurodevelopmental syndrome; Wilms tumour predisposition
Mendeliome v0.8307 FBXW7 Zornitza Stark Publications for gene: FBXW7 were set to 33057194
Mendeliome v0.8306 FBXW7 Zornitza Stark reviewed gene: FBXW7: Rating: GREEN; Mode of pathogenicity: None; Publications: 30885698, 26482194; Phenotypes: Wilms tumour predisposition; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8306 NYNRIN Laura Raiti gene: NYNRIN was added
gene: NYNRIN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NYNRIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NYNRIN were set to PMID: 30885698
Review for gene: NYNRIN was set to AMBER
Added comment: 3 individuals with Wilms Tumour reported (2 children from 1 family, the 3rd child from a second family).
Biallelic truncating mutations in NYNRIN in three children with Wilms Tumour from two families, each parent was heterozygous for one of the mutations.
One of the affected children had an inguinal hernia and another had epilepsy, hypothyroidism, and intellectual disability.
Sources: Literature
Mendeliome v0.8306 YARS Zornitza Stark Phenotypes for gene: YARS were changed from Charcot-Marie-Tooth disease, dominant intermediate C 608323; Bi-allelic variants: ID, deafness, nystagmus to Charcot-Marie-Tooth disease, dominant intermediate C, MIM# 608323; MONDO:0012012; Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2, MIM# 619418
Mendeliome v0.8305 YARS Zornitza Stark changed review comment from: More than 5 unrelated families reported.; to: Mono-allelic disease: More than 5 unrelated families reported.
Mendeliome v0.8305 YARS Zornitza Stark edited their review of gene: YARS: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8305 YARS Zornitza Stark edited their review of gene: YARS: Changed phenotypes: Charcot-Marie-Tooth disease, dominant intermediate C, MIM# 608323, MONDO:0012012, Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2, MIM# 619418
Mendeliome v0.8305 ZC3H14 Zornitza Stark Publications for gene: ZC3H14 were set to 21734151; 28666327
Mendeliome v0.8304 ZC3H14 Zornitza Stark edited their review of gene: ZC3H14: Added comment: PMID: 33710394
1 Finnish family with a hom splice variant, severe ID. Classed a VUS. No functional evidence; Changed publications: 21734151, 28666327, 33710394
Mendeliome v0.8304 ZC3H14 Zornitza Stark Deleted their comment
Mendeliome v0.8304 ZC3H14 Zornitza Stark edited their review of gene: ZC3H14: Added comment: Two families and a mouse model.; Changed phenotypes: Mental retardation, autosomal recessive 56, OMIM# 617125
Mendeliome v0.8304 ZC3H14 Zornitza Stark edited their review of gene: ZC3H14: Changed publications: 21734151, 28666327
Mendeliome v0.8304 ZC3H14 Zornitza Stark edited their review of gene: ZC3H14: Changed rating: AMBER; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8304 ZC3H14 Zornitza Stark Publications for gene: ZC3H14 were set to 21734151
Mendeliome v0.8303 ZC3H14 Zornitza Stark Mode of inheritance for gene: ZC3H14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8302 ATP1A2 Zornitza Stark Marked gene: ATP1A2 as ready
Mendeliome v0.8302 ATP1A2 Zornitza Stark Gene: atp1a2 has been classified as Green List (High Evidence).
Mendeliome v0.8302 RNF2 Zornitza Stark Marked gene: RNF2 as ready
Mendeliome v0.8302 RNF2 Zornitza Stark Gene: rnf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8302 RNF2 Zornitza Stark Classified gene: RNF2 as Amber List (moderate evidence)
Mendeliome v0.8302 RNF2 Zornitza Stark Gene: rnf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8301 RING1 Zornitza Stark Marked gene: RING1 as ready
Mendeliome v0.8301 RING1 Zornitza Stark Gene: ring1 has been classified as Red List (Low Evidence).
Mendeliome v0.8301 RING1 Zornitza Stark Classified gene: RING1 as Red List (low evidence)
Mendeliome v0.8301 RING1 Zornitza Stark Gene: ring1 has been classified as Red List (Low Evidence).
Mendeliome v0.8300 IRX5 Zornitza Stark Marked gene: IRX5 as ready
Mendeliome v0.8300 IRX5 Zornitza Stark Gene: irx5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8300 IRX5 Zornitza Stark Tag SV/CNV tag was added to gene: IRX5.
Mendeliome v0.8300 IRX5 Zornitza Stark Phenotypes for gene: IRX5 were changed from to Hamamy syndrome, MIM# 611174; cone dystrophy, MONDO:0000455
Mendeliome v0.8299 IRX5 Zornitza Stark Publications for gene: IRX5 were set to
Mendeliome v0.8298 IRX5 Zornitza Stark Mode of inheritance for gene: IRX5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8297 IRX5 Zornitza Stark Classified gene: IRX5 as Amber List (moderate evidence)
Mendeliome v0.8297 IRX5 Zornitza Stark Gene: irx5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8296 IRX5 Zornitza Stark edited their review of gene: IRX5: Changed rating: AMBER
Mendeliome v0.8296 IRX5 Zornitza Stark reviewed gene: IRX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22581230, 27453922; Phenotypes: Hamamy syndrome, MIM# 611174; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8296 IRX6 Zornitza Stark reviewed gene: IRX6: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8296 IRX6 Zornitza Stark Marked gene: IRX6 as ready
Mendeliome v0.8296 IRX6 Zornitza Stark Gene: irx6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8296 IRX6 Zornitza Stark Classified gene: IRX6 as Amber List (moderate evidence)
Mendeliome v0.8296 IRX6 Zornitza Stark Gene: irx6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8295 RAB3GAP1 Zornitza Stark Phenotypes for gene: RAB3GAP1 were changed from Warburg micro syndrome 1, MIM# 600118 to Warburg micro syndrome 1, MIM# 600118; Martsolf syndrome 2, MIM# 619420
Mendeliome v0.8294 RAB3GAP1 Zornitza Stark Publications for gene: RAB3GAP1 were set to 15696165; 20512159; 23420520
Mendeliome v0.8293 RAB3GAP1 Zornitza Stark changed review comment from: Rare autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism. Multiple families reported.; to: Warburg micro: Rare autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe ID, spastic diplegia, and hypogonadism. Multiple families reported.

Martsolf syndrome is characterised by cataracts, mild to severe ID, dysmorphic features. Two families reported.
Mendeliome v0.8293 RAB3GAP1 Zornitza Stark edited their review of gene: RAB3GAP1: Changed publications: 15696165, 20512159, 23420520, 23420520, 30730599; Changed phenotypes: Warburg micro syndrome 1, MIM# 600118, Martsolf syndrome 2, MIM# 619420
Mendeliome v0.8293 CXCR2 Zornitza Stark Marked gene: CXCR2 as ready
Mendeliome v0.8293 CXCR2 Zornitza Stark Gene: cxcr2 has been classified as Red List (Low Evidence).
Mendeliome v0.8293 CXCR2 Zornitza Stark gene: CXCR2 was added
gene: CXCR2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CXCR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CXCR2 were set to 24777453
Phenotypes for gene: CXCR2 were set to WHIM syndrome 2, 619407
Review for gene: CXCR2 was set to RED
Added comment: 2 sisters with neutropaenia, myelokathexis, and recurrent bacterial infections and homozygous frameshift variant in this gene.
Sources: Expert list
Mendeliome v0.8292 RING1 Eleanor Williams gene: RING1 was added
gene: RING1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RING1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RING1 were set to 29386386
Phenotypes for gene: RING1 were set to microcephaly; intellectual disability
Review for gene: RING1 was set to RED
Added comment: Not associated with any phenotype in OMIM.

PMID: 29386386 - Pierce et al 2018 - report a 13 yo female with a de novo RING1 p.R95Q variant and syndromic neurodevelopmental disabilities. Early motor and language development were normal but were delayed after the first year of life. Cognitive testing showed a verbal IQ of 55 and a visual performance IQ of 63. Head circumference at birth was -4.9 SD, and -4.2 SD at age 13 which falls into the severe microcephaly category. C. elegans with either the missense mutation or complete knockout of spat-3 (the suggested RING1 ortholog) were defective in monoubiquitylation of histone H2A and had defects in neuronal migration and axon guidance.
Sources: Literature
Mendeliome v0.8292 RNF2 Eleanor Williams gene: RNF2 was added
gene: RNF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RNF2 were set to 33864376
Phenotypes for gene: RNF2 were set to epilepsy; intellectual disability; intrauterine growth retardation
Review for gene: RNF2 was set to AMBER
Added comment: Not associated with any phenotype in OMIM.

PMID:33864376 (Luo et al 2021) report 2 cases of children with de novo missense variants (p.R70H and p.S82R) in RNF2 and a phenotype of intrauterine growth retardation, severe intellectual disabilities, behavioral problems, seizures, feeding difficulties and dysmorphic features. Seizures started in infancy. Both variants are absent from gnomad. Functional studies in Drosophila showed that the disease-linked variants (p.R70H and p.S82R) behave as LoF alleles.
Sources: Literature
Mendeliome v0.8292 IRX5 Eleanor Williams edited their review of gene: IRX5: Changed publications: 33891002, 28041643, 32045705, 22581230, 17230486; Changed phenotypes: cone dystrophy, MONDO:0000455, retinitis pigmentosa, MONDO:0019200
Mendeliome v0.8292 IRX5 Eleanor Williams changed review comment from: Associated with Hamamy syndrome #611174 (AR) in OMIM. Hamamy syndrome is characterised by craniofacial dysmorphism, hearing loss, skeletal anomalies, microcytic hypochromic anemia and congenital heart defects. Severe myopia has also been reported. Homozygous missense variants in IRX5 were reported in 2 families with this condition.

Cone dystrophy
-------------------
PMID: 33891002 - Khol et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.; to: Associated with Hamamy syndrome #611174 (AR) in OMIM. Hamamy syndrome is characterised by craniofacial dysmorphism, hearing loss, skeletal anomalies, microcytic hypochromic anemia and congenital heart defects. Severe myopia has also been reported. Homozygous missense variants in IRX5 were reported in 2 families with this condition (PMID: 22581230;17230486)

Duplication of gene
-------------------
PMID: 33891002 - Kohl et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.

Loss of function/gene
---------
PMID: 28041643 - Carss et al 2017 - screened a cohort of 722 individuals with inherited retinal disease using WES/WGS. 1 case reported with a biallelic deletion in IRX5 reported which leads to a frameshift ENST00000394636.4; c.1362_1366delTAAAG, p.Lys455ProfsTer19 in a patient with retinitis pigmentosa.

PMID: 32045705 - Apuzzo et al 2020 - report 2 cases of loss of a region in 16q12.1q21 which encompasses IRX5 and IRX6 and many other genes, which together with 3 other previous reports of deletions in this region help define a syndrome with features that include dysmorphic features, short stature, microcephaly, global developmental delay/intellectual disability, autism spectrum disorder (ASD) and ocular abnormalities (nystagmus and strabismus).
Mendeliome v0.8292 IRX6 Eleanor Williams changed review comment from: Not associated with any disorder in OMIM or Gene2Phenotype.

PMID: 33891002 - Khol et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.
Sources: Literature; to: Not associated with any disorder in OMIM or Gene2Phenotype.

PMID: 33891002 - Kohl et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.
Sources: Literature
Mendeliome v0.8292 SLCO2A1 Zornitza Stark Marked gene: SLCO2A1 as ready
Mendeliome v0.8292 SLCO2A1 Zornitza Stark Gene: slco2a1 has been classified as Green List (High Evidence).
Mendeliome v0.8292 GNB2 Zornitza Stark Publications for gene: GNB2 were set to 31698099
Mendeliome v0.8291 GNB2 Zornitza Stark Classified gene: GNB2 as Green List (high evidence)
Mendeliome v0.8291 GNB2 Zornitza Stark Gene: gnb2 has been classified as Green List (High Evidence).
Mendeliome v0.8290 GNB2 Zornitza Stark reviewed gene: GNB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31698099, 33971351, 34183358; Phenotypes: Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8290 HID1 Zornitza Stark Marked gene: HID1 as ready
Mendeliome v0.8290 HID1 Zornitza Stark Gene: hid1 has been classified as Green List (High Evidence).
Mendeliome v0.8290 HID1 Zornitza Stark Classified gene: HID1 as Green List (high evidence)
Mendeliome v0.8290 HID1 Zornitza Stark Gene: hid1 has been classified as Green List (High Evidence).
Mendeliome v0.8289 HID1 Zornitza Stark gene: HID1 was added
gene: HID1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HID1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HID1 were set to 33999436
Phenotypes for gene: HID1 were set to Syndromic infantile encephalopathy; Hypopituitarism
Review for gene: HID1 was set to GREEN
Added comment: 7 individuals from 6 unrelated families reported. Clinical features included: hypopituitarism in combination with brain atrophy, thin corpus callosum, severe developmental delay, visual impairment, and epilepsy
Sources: Literature
Mendeliome v0.8288 KIF1B Zornitza Stark Marked gene: KIF1B as ready
Mendeliome v0.8288 KIF1B Zornitza Stark Gene: kif1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8288 KIF1B Zornitza Stark Phenotypes for gene: KIF1B were changed from to Charcot-Marie-Tooth disease, type 2A1 MIM#118210; Hypotonia, coloboma, hypoplasia of the corpus callosum, severe neurodevelopmental delay
Mendeliome v0.8287 KIF1B Zornitza Stark Publications for gene: KIF1B were set to
Mendeliome v0.8286 KIF1B Zornitza Stark Mode of inheritance for gene: KIF1B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8285 KIF1B Zornitza Stark reviewed gene: KIF1B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8285 NUF2 Zornitza Stark Marked gene: NUF2 as ready
Mendeliome v0.8285 NUF2 Zornitza Stark Gene: nuf2 has been classified as Red List (Low Evidence).
Mendeliome v0.8285 NUF2 Zornitza Stark Classified gene: NUF2 as Red List (low evidence)
Mendeliome v0.8285 NUF2 Zornitza Stark Gene: nuf2 has been classified as Red List (Low Evidence).
Mendeliome v0.8284 ERGIC3 Seb Lunke Marked gene: ERGIC3 as ready
Mendeliome v0.8284 ERGIC3 Seb Lunke Gene: ergic3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8284 ERGIC3 Seb Lunke Classified gene: ERGIC3 as Amber List (moderate evidence)
Mendeliome v0.8284 ERGIC3 Seb Lunke Gene: ergic3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8283 FYCO1 Zornitza Stark Marked gene: FYCO1 as ready
Mendeliome v0.8283 FYCO1 Zornitza Stark Gene: fyco1 has been classified as Green List (High Evidence).
Mendeliome v0.8283 FYCO1 Zornitza Stark Phenotypes for gene: FYCO1 were changed from to Cataract 18, MIM#610019
Mendeliome v0.8282 FYCO1 Zornitza Stark Publications for gene: FYCO1 were set to
Mendeliome v0.8281 FYCO1 Zornitza Stark Mode of inheritance for gene: FYCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8280 FYCO1 Zornitza Stark reviewed gene: FYCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32355443; Phenotypes: Cataract 18, MIM#610019; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8280 JPH3 Seb Lunke Publications for gene: JPH3 were set to
Mendeliome v0.8279 MYT1 Zornitza Stark Publications for gene: MYT1 were set to 28612832; 32871052; 27358179
Mendeliome v0.8278 JPH3 Seb Lunke Marked gene: JPH3 as ready
Mendeliome v0.8278 JPH3 Seb Lunke Gene: jph3 has been classified as Red List (Low Evidence).
Mendeliome v0.8278 JPH3 Seb Lunke Phenotypes for gene: JPH3 were changed from to Intellectual disability; dystonia
Mendeliome v0.8277 MYT1 Zornitza Stark changed review comment from: Five unrelated individuals reported with variants in this gene and OAV spectrum.; to: Five unrelated individuals reported with variants in this gene and OAV spectrum.

Single individual reported with missense variant as part of an ID cohort, limited evidence for disease association.
Mendeliome v0.8277 JPH3 Seb Lunke Classified gene: JPH3 as Red List (low evidence)
Mendeliome v0.8277 JPH3 Seb Lunke Added comment: Comment on list classification: Only STRs disease causing, see separate STR list. No evidence for SNVs etc.
Mendeliome v0.8277 JPH3 Seb Lunke Gene: jph3 has been classified as Red List (Low Evidence).
Mendeliome v0.8276 MYT1 Zornitza Stark edited their review of gene: MYT1: Changed publications: 28612832, 32871052, 27358179, 33710394
Mendeliome v0.8276 MYT1 Zornitza Stark Marked gene: MYT1 as ready
Mendeliome v0.8276 MYT1 Zornitza Stark Gene: myt1 has been classified as Green List (High Evidence).
Mendeliome v0.8276 MYT1 Zornitza Stark Phenotypes for gene: MYT1 were changed from to Craniofacial microsomia; OAV spectrum
Mendeliome v0.8275 MYT1 Zornitza Stark Publications for gene: MYT1 were set to
Mendeliome v0.8274 MYT1 Zornitza Stark Mode of inheritance for gene: MYT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8273 MYT1 Zornitza Stark reviewed gene: MYT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28612832, 32871052, 27358179; Phenotypes: Craniofacial microsomia, OAV spectrum; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8273 HEATR5B Seb Lunke Phenotypes for gene: HEATR5B were changed from pontocerebellar hypoplasia to pontocerebellar hypoplasia; intellectual disability; seizures
Mendeliome v0.8272 ATP1A2 Zornitza Stark Phenotypes for gene: ATP1A2 were changed from to Alternating hemiplegia of childhood 1, MIM#104290; Hydrops fetalis, microcephaly, arthrogryposis, extensive cortical malformations; Developmental and epileptic encephalopathy, polymicrogyria
Mendeliome v0.8271 ATP1A2 Zornitza Stark Publications for gene: ATP1A2 were set to
Mendeliome v0.8270 ATP1A2 Zornitza Stark Mode of inheritance for gene: ATP1A2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8269 ATP1A2 Zornitza Stark edited their review of gene: ATP1A2: Added comment: Association with alternating hemiplegia is well established.

PMID 31608932: Three individuals from two unrelated families reported with balleliic LoF variants in this gene and hydrops/congenital abnormalities. Mouse model is perinatal lethal.

PMID 33880529: six individuals with de novo missense variants reported and DD/EE/PMG.; Changed rating: GREEN; Changed publications: 31608932, 33880529; Changed phenotypes: Alternating hemiplegia of childhood 1, MIM#104290, Hydrops fetalis, microcephaly, arthrogryposis, extensive cortical malformations, Developmental and epileptic encephalopathy, polymicrogyria; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8269 HEATR5B Seb Lunke Marked gene: HEATR5B as ready
Mendeliome v0.8269 HEATR5B Seb Lunke Gene: heatr5b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8269 HEATR5B Seb Lunke Classified gene: HEATR5B as Amber List (moderate evidence)
Mendeliome v0.8269 HEATR5B Seb Lunke Gene: heatr5b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8268 ATP1A3 Zornitza Stark edited their review of gene: ATP1A3: Changed phenotypes: Alternating hemiplegia of childhood 2, MIM# 614820, CAPOS syndrome, MIM# 601338, Dystonia-12, MIM# 128235, Polymicrogyria, Developmental and epileptic encephalopathy
Mendeliome v0.8268 ATP1A3 Zornitza Stark edited their review of gene: ATP1A3: Changed publications: 15260953, 22842232, 24468074, 33762331, 33880529
Mendeliome v0.8268 SAMD9L Zornitza Stark Phenotypes for gene: SAMD9L were changed from Ataxia-pancytopenia syndrome, MIM# 159550 to Ataxia-pancytopenia syndrome, MIM# 159550; Intellectual disability
Mendeliome v0.8267 SAMD9L Zornitza Stark Publications for gene: SAMD9L were set to 27259050; 30923096; 30322869
Mendeliome v0.8266 SAMD9L Zornitza Stark changed review comment from: At least three unrelated families reported, some postulate GoF whereas others postulate LoF as mechanism.; to: Ataxia-pancytopaenia: At least three unrelated families reported, some postulate GoF whereas others postulate LoF as mechanism.

ID: single individual reported, limited evidence of association.
Mendeliome v0.8266 SAMD9L Zornitza Stark edited their review of gene: SAMD9L: Changed publications: 27259050, 30923096, 30322869, 33710394
Mendeliome v0.8266 PITRM1 Zornitza Stark Phenotypes for gene: PITRM1 were changed from Ataxia; Intellectual disability to Spinocerebellar ataxia-30 (SCAR30), MIM#619405; intellectual disability; cognitive decline; psychosis
Mendeliome v0.8265 PITRM1 Zornitza Stark edited their review of gene: PITRM1: Changed phenotypes: Spinocerebellar ataxia-30 (SCAR30), MIM#619405
Mendeliome v0.8265 VPS41 Zornitza Stark Phenotypes for gene: VPS41 were changed from Dystonia; intellectual disability to Spinocerebellar ataxia-29 (SCAR29), MIM#619389; Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay
Mendeliome v0.8264 IRX6 Eleanor Williams gene: IRX6 was added
gene: IRX6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IRX6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IRX6 were set to 33891002
Phenotypes for gene: IRX6 were set to cone dystrophy, MONDO:0000455
Mode of pathogenicity for gene: IRX6 was set to Other
Review for gene: IRX6 was set to GREEN
Added comment: Not associated with any disorder in OMIM or Gene2Phenotype.

PMID: 33891002 - Khol et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.
Sources: Literature
Mendeliome v0.8264 IRX5 Eleanor Williams reviewed gene: IRX5: Rating: GREEN; Mode of pathogenicity: Other; Publications: 33891002; Phenotypes: cone dystrophy, MONDO:0000455; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.8264 EPHA7 Zornitza Stark Tag SV/CNV tag was added to gene: EPHA7.
Mendeliome v0.8264 EPHA7 Zornitza Stark Marked gene: EPHA7 as ready
Mendeliome v0.8264 EPHA7 Zornitza Stark Gene: epha7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8264 EPHA7 Zornitza Stark Classified gene: EPHA7 as Amber List (moderate evidence)
Mendeliome v0.8264 EPHA7 Zornitza Stark Gene: epha7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8263 EPHA7 Zornitza Stark gene: EPHA7 was added
gene: EPHA7 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: EPHA7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EPHA7 were set to 34176129
Phenotypes for gene: EPHA7 were set to Intellectual disability
Review for gene: EPHA7 was set to AMBER
Added comment: Lévy et al (2021 - PMID: 34176129) provide evidence that haploinssuficiency of EPHA7 results in a neurodevelopmental disorder.

The authors report on 12 individuals belonging to 9 unrelated families, all harboring with 6q microdeletions spanning EPHA7.

Overlapping features included DD (13/13), ID (10/10 - mild in most cases, individuals with larger CNVs/additional variants had more severe phenotype), speech delay and behavioral disorders. Variable other features incl. hypotonia (70%), non specific facial features, eye abnormalities (40%) and cardiac defects (25%).

The CNVs ranged from 152 kb to few Mb in size but in 4 subjects (P5-8) were only minimal, involving only EPHA7.

9 out of 12 individuals had inherited the deletion (5 subjects paternal, 4 maternal), in 1 subject (P12) this occured de novo, while for 2 others inheritance was not specified. Most deletions were inherited from an unaffected parent (in 6/7 families), with unclear contribution in a further one.

The authors discuss on previous studies suggesting an important role for EphA7 in brain development (modulation of cell-cell adhesion and repulsion, regulation of dendrite morphogenesis in early corticogenesis, role in dendritic spine formation later in development. EphA7 has also been proposed to drive neuronal maturation and synaptic function).

Haploinsufficiency for other ephrins or ephrin receptors has been implicated in other NDDs.

Overall Lévy et al promote incomplete penetrance and variable expressivity with haploinsufficiency of this gene being a risk factor for NDD. [The gene has also an %HI of 2.76% and a pLI of 1].
Sources: Expert Review
Mendeliome v0.8262 DNM1 Zornitza Stark Marked gene: DNM1 as ready
Mendeliome v0.8262 DNM1 Zornitza Stark Gene: dnm1 has been classified as Green List (High Evidence).
Mendeliome v0.8262 DNM1 Zornitza Stark Phenotypes for gene: DNM1 were changed from to Developmental and epileptic encephalopathy 31, OMIM:616346
Mendeliome v0.8261 DNM1 Zornitza Stark Publications for gene: DNM1 were set to
Mendeliome v0.8260 DNM1 Zornitza Stark Mode of inheritance for gene: DNM1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8259 DNM1 Zornitza Stark reviewed gene: DNM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25262651, 27066543, 33372033, 34172529; Phenotypes: Developmental and epileptic encephalopathy 31, OMIM:616346; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8259 GRK2 Zornitza Stark Marked gene: GRK2 as ready
Mendeliome v0.8259 GRK2 Zornitza Stark Gene: grk2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8259 GRK2 Zornitza Stark Classified gene: GRK2 as Amber List (moderate evidence)
Mendeliome v0.8259 GRK2 Zornitza Stark Gene: grk2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8258 GRK2 Zornitza Stark gene: GRK2 was added
gene: GRK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GRK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRK2 were set to 33200460
Phenotypes for gene: GRK2 were set to Jeune asphyxiating thoracic dystrophy (ATD)
Review for gene: GRK2 was set to AMBER
Added comment: Two unrelated families reported and some functional data.
Sources: Literature
Mendeliome v0.8257 WDR60 Zornitza Stark Marked gene: WDR60 as ready
Mendeliome v0.8257 WDR60 Zornitza Stark Gene: wdr60 has been classified as Green List (High Evidence).
Mendeliome v0.8257 WDR60 Zornitza Stark Phenotypes for gene: WDR60 were changed from to Short-rib thoracic dysplasia 8 with or without polydactyly, MIM# 615503; Retinitis pigmentosa
Mendeliome v0.8256 WDR60 Zornitza Stark Publications for gene: WDR60 were set to
Mendeliome v0.8255 WDR60 Zornitza Stark Mode of inheritance for gene: WDR60 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8254 WDR60 Zornitza Stark reviewed gene: WDR60: Rating: GREEN; Mode of pathogenicity: None; Publications: 23910462, 29271569, 26874042; Phenotypes: Short-rib thoracic dysplasia 8 with or without polydactyly, MIM# 615503, Retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8254 WDR34 Zornitza Stark Marked gene: WDR34 as ready
Mendeliome v0.8254 WDR34 Zornitza Stark Gene: wdr34 has been classified as Green List (High Evidence).
Mendeliome v0.8254 WDR34 Zornitza Stark Phenotypes for gene: WDR34 were changed from to Short-rib thoracic dysplasia 11 with or without polydactyly, MIM# 615633; Retinitis pigmentosa
Mendeliome v0.8253 WDR34 Zornitza Stark Publications for gene: WDR34 were set to
Mendeliome v0.8252 WDR34 Zornitza Stark Mode of inheritance for gene: WDR34 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8251 WDR34 Zornitza Stark reviewed gene: WDR34: Rating: GREEN; Mode of pathogenicity: None; Publications: 24183449, 24183451, 33124039, 30649997, 29241935, 28379358; Phenotypes: Short-rib thoracic dysplasia 11 with or without polydactyly, MIM# 615633, Retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8251 WDR19 Zornitza Stark Marked gene: WDR19 as ready
Mendeliome v0.8251 WDR19 Zornitza Stark Gene: wdr19 has been classified as Green List (High Evidence).
Mendeliome v0.8251 WDR19 Zornitza Stark Phenotypes for gene: WDR19 were changed from to Nephronophthisis 13, MIM# 614377; Senior-Loken syndrome 8, MIM# 616307; Short-rib thoracic dysplasia 5 with or without polydactyly, MIM# 614376; Cranioectodermal dysplasia 4, MIM# 614378
Mendeliome v0.8250 WDR19 Zornitza Stark Publications for gene: WDR19 were set to
Mendeliome v0.8249 WDR19 Zornitza Stark Mode of inheritance for gene: WDR19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8248 WDR19 Zornitza Stark reviewed gene: WDR19: Rating: GREEN; Mode of pathogenicity: None; Publications: 33946315, 33875766, 33606107, 22019273, 23559409, 23683095, 32055034; Phenotypes: Nephronophthisis 13, MIM# 614377, Senior-Loken syndrome 8, MIM# 616307, Short-rib thoracic dysplasia 5 with or without polydactyly, MIM# 614376, Cranioectodermal dysplasia 4, MIM# 614378; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8248 TXNDC15 Zornitza Stark Marked gene: TXNDC15 as ready
Mendeliome v0.8248 TXNDC15 Zornitza Stark Gene: txndc15 has been classified as Green List (High Evidence).
Mendeliome v0.8248 TXNDC15 Zornitza Stark Phenotypes for gene: TXNDC15 were changed from to Meckel-Gruber syndrome
Mendeliome v0.8247 TXNDC15 Zornitza Stark Publications for gene: TXNDC15 were set to
Mendeliome v0.8246 TXNDC15 Zornitza Stark Mode of inheritance for gene: TXNDC15 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8245 TXNDC15 Zornitza Stark reviewed gene: TXNDC15: Rating: GREEN; Mode of pathogenicity: None; Publications: 30851085, 27894351; Phenotypes: Meckel-Gruber syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8245 TTC8 Zornitza Stark Marked gene: TTC8 as ready
Mendeliome v0.8245 TTC8 Zornitza Stark Gene: ttc8 has been classified as Green List (High Evidence).
Mendeliome v0.8245 TTC8 Zornitza Stark Phenotypes for gene: TTC8 were changed from to Bardet-Biedl syndrome 8, MIM# 615985
Mendeliome v0.8244 TTC8 Zornitza Stark Publications for gene: TTC8 were set to
Mendeliome v0.8243 TTC8 Zornitza Stark Mode of inheritance for gene: TTC8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8242 TTC8 Zornitza Stark reviewed gene: TTC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 14520415, 19797195; Phenotypes: Bardet-Biedl syndrome 8, MIM# 615985; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8242 TTC21B Zornitza Stark Marked gene: TTC21B as ready
Mendeliome v0.8242 TTC21B Zornitza Stark Gene: ttc21b has been classified as Green List (High Evidence).
Mendeliome v0.8242 TTC21B Zornitza Stark Phenotypes for gene: TTC21B were changed from to Nephronophthisis 12, MIM# 613820; Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819; Joubert syndrome
Mendeliome v0.8241 TTC21B Zornitza Stark Publications for gene: TTC21B were set to
Mendeliome v0.8240 TTC21B Zornitza Stark Mode of inheritance for gene: TTC21B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8239 TTC21B Zornitza Stark reviewed gene: TTC21B: Rating: GREEN; Mode of pathogenicity: None; Publications: 21258341, 25492405, 18327258, 33875766; Phenotypes: Nephronophthisis 12, MIM# 613820, Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819, Joubert syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8239 TRAF3IP1 Zornitza Stark Marked gene: TRAF3IP1 as ready
Mendeliome v0.8239 TRAF3IP1 Zornitza Stark Gene: traf3ip1 has been classified as Green List (High Evidence).
Mendeliome v0.8239 TRAF3IP1 Zornitza Stark Phenotypes for gene: TRAF3IP1 were changed from to Senior-Loken syndrome 9, MIM# 616629; MONDO:0014712
Mendeliome v0.8238 TRAF3IP1 Zornitza Stark Publications for gene: TRAF3IP1 were set to
Mendeliome v0.8237 TRAF3IP1 Zornitza Stark Mode of inheritance for gene: TRAF3IP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8236 TRAF3IP1 Zornitza Stark reviewed gene: TRAF3IP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26487268, 18364699, 21945076; Phenotypes: Senior-Loken syndrome 9, MIM# 616629, MONDO:0014712; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8236 ATP9A Zornitza Stark Classified gene: ATP9A as Amber List (moderate evidence)
Mendeliome v0.8236 ATP9A Zornitza Stark Gene: atp9a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8235 ATP2C2 Zornitza Stark Classified gene: ATP2C2 as Red List (low evidence)
Mendeliome v0.8235 ATP2C2 Zornitza Stark Gene: atp2c2 has been classified as Red List (Low Evidence).
Mendeliome v0.8234 OBSCN Zornitza Stark Tag refuted was removed from gene: OBSCN.
Tag disputed tag was added to gene: OBSCN.
Mendeliome v0.8234 OBSCN Zornitza Stark Publications for gene: OBSCN were set to 30681346; 26573135; 17716621; 25173926; 28630914
Mendeliome v0.8233 OBSCN Zornitza Stark Tag refuted tag was added to gene: OBSCN.
Mendeliome v0.8233 P2RX2 Zornitza Stark Publications for gene: P2RX2 were set to 23345450; 24211385
Mendeliome v0.8232 AP2S1 Zornitza Stark Publications for gene: AP2S1 were set to 33729479; 33057194; 23222959; 33729479; 33168530; 3204769; 31723423; 29479578
Mendeliome v0.8231 AP2S1 Zornitza Stark Publications for gene: AP2S1 were set to 33729479; 33057194; 23222959; 33729479; 33168530; 3204769; 31723423; 2947957; 8
Mendeliome v0.8230 AP2S1 Zornitza Stark Publications for gene: AP2S1 were set to 33057194; 23222959; 33729479; 33168530; 3204769; 31723423; 29479578
Mendeliome v0.8229 ATP9A Arina Puzriakova gene: ATP9A was added
gene: ATP9A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP9A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP9A were set to http://dx.doi.org/10.1136/jmedgenet-2021-107843
Phenotypes for gene: ATP9A were set to Neurodevelopmental delay; Postnatal microcephaly; Failure to thrive; Gastrointestinal symptoms
Review for gene: ATP9A was set to AMBER
Added comment: Vogt et al. 2021 report on 3 individuals from 2 unrelated consanguineous families with different homozygous truncating variants in ATP9A, presenting with DD/ID of variable degree (2 mild, 1 severe), postnatal microcephaly (OFC range: −2.33 SD to −3.58 SD), failure to thrive, and gastrointestinal symptoms. Patient-derived fibroblasts showed reduced expression of ATP9A, and consistent with previous findings also overexpression of interacting partners, ARPC3 and SNX3.
Sources: Literature
Mendeliome v0.8229 ATP2C2 Eleanor Williams gene: ATP2C2 was added
gene: ATP2C2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP2C2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATP2C2 were set to 33864365; 28440294
Phenotypes for gene: ATP2C2 were set to language impairment, HP:0002463
Review for gene: ATP2C2 was set to RED
Added comment: PMID: 33864365 - Martinelli et al 2021 - report a family with a missense variant NM_001286527.2:c.304G>A, p.(Val102Met) in ATP2C2 in a father and two siblings with specific language impairment. However two other affected siblings did not have this variant. This variant was also reported by Chen et al. They found that the variant had a higher frequency in language cases (1.8%, N = 360) compared with cohorts selected for dyslexia (0.8%, N = 520) and ADHD (0.7%, N = 150), which presented frequencies comparable to reference databases (0.9%, N = 24 046 gnomAD controls). They postulate that variant is not sufficient on its own to cause a disorder but is a susceptibility factor which increases the risk for language impairment.

PMID: 28440294 - Chen et al 2017 - report 2 probands with severe learning impairment, and missense variants in ATP2C2 (NM_001286527: c.G304A:p.V102M and NM_001291454:exon21: c.C1936T:p.R646W).
Sources: Literature
Mendeliome v0.8229 OBSCN Eleanor Williams reviewed gene: OBSCN: Rating: RED; Mode of pathogenicity: None; Publications: 33438037; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.8229 P2RX2 Eleanor Williams reviewed gene: P2RX2: Rating: ; Mode of pathogenicity: None; Publications: 33791800; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.8229 AP2S1 Eleanor Williams reviewed gene: AP2S1: Rating: ; Mode of pathogenicity: None; Publications: 33729479; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.8229 TMEM67 Zornitza Stark Marked gene: TMEM67 as ready
Mendeliome v0.8229 TMEM67 Zornitza Stark Gene: tmem67 has been classified as Green List (High Evidence).
Mendeliome v0.8229 TMEM67 Zornitza Stark Phenotypes for gene: TMEM67 were changed from to Joubert syndrome 6, MIM# 610688; Meckel syndrome 3, MIM# 607361; Nephronophthisis 11, MIM# 613550; COACH syndrome 1, MIM# 216360
Mendeliome v0.8228 TMEM67 Zornitza Stark Publications for gene: TMEM67 were set to
Mendeliome v0.8227 TMEM67 Zornitza Stark Mode of inheritance for gene: TMEM67 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8226 TMEM67 Zornitza Stark Deleted their comment
Mendeliome v0.8226 TMEM67 Zornitza Stark edited their review of gene: TMEM67: Added comment: Bi-allelic variants in this gene are associated with a range of ciliopathies, including JBTS, Meckel syndrome and nephronophthisis. Multiple families with each.; Changed publications: 16415887, 17377820, 17160906, 19508969; Changed phenotypes: Joubert syndrome 6, MIM# 610688, Meckel syndrome 3, MIM# 607361, Nephronophthisis 11, MIM# 613550, COACH syndrome 1, MIM# 216360
Mendeliome v0.8226 XDH Zornitza Stark Marked gene: XDH as ready
Mendeliome v0.8226 XDH Zornitza Stark Gene: xdh has been classified as Green List (High Evidence).
Mendeliome v0.8226 XDH Zornitza Stark Phenotypes for gene: XDH were changed from to Xanthinuria, type I (MIM#278300)
Mendeliome v0.8225 XDH Zornitza Stark Publications for gene: XDH were set to
Mendeliome v0.8224 XDH Zornitza Stark Mode of inheritance for gene: XDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8223 XDH Ain Roesley reviewed gene: XDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 32071838; Phenotypes: Xanthinuria, type I (MIM#278300); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.8223 TCTEX1D2 Zornitza Stark Marked gene: TCTEX1D2 as ready
Mendeliome v0.8223 TCTEX1D2 Zornitza Stark Gene: tctex1d2 has been classified as Green List (High Evidence).
Mendeliome v0.8223 TCTEX1D2 Zornitza Stark Phenotypes for gene: TCTEX1D2 were changed from to Short-rib thoracic dysplasia 17 with or without polydactyly, MIM# 617405
Mendeliome v0.8222 TCTEX1D2 Zornitza Stark Publications for gene: TCTEX1D2 were set to
Mendeliome v0.8221 TCTEX1D2 Zornitza Stark Mode of inheritance for gene: TCTEX1D2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8220 TCTEX1D2 Zornitza Stark reviewed gene: TCTEX1D2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26044572, 25830415; Phenotypes: Short-rib thoracic dysplasia 17 with or without polydactyly, MIM# 617405; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8220 TCTN3 Zornitza Stark Marked gene: TCTN3 as ready
Mendeliome v0.8220 TCTN3 Zornitza Stark Gene: tctn3 has been classified as Green List (High Evidence).
Mendeliome v0.8220 TCTN3 Zornitza Stark Phenotypes for gene: TCTN3 were changed from to Joubert syndrome 18, MIM# 614815; MONDO:0013896; Orofaciodigital syndrome IV, MIM# 258860; Mohr-Majewski syndrome; Meckel-Gruber syndrome
Mendeliome v0.8219 TCTN3 Zornitza Stark Publications for gene: TCTN3 were set to
Mendeliome v0.8218 TCTN3 Zornitza Stark Mode of inheritance for gene: TCTN3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8217 TCTN3 Zornitza Stark changed review comment from: Rare cause of JBS, I can only find two families reported plus one with OFD. Ataxia specifically described in one of the JBS individuals.; to: Three unrelated families reported with JBTS phenotype. Variants in this gene are associated with other ciliopathies as well (OFD and Mohr-Majewski).
Mendeliome v0.8217 TCTN3 Zornitza Stark edited their review of gene: TCTN3: Changed publications: 22883145, 32139166, 25118024, 34096792; Changed phenotypes: Joubert syndrome 18, MIM# 614815, MONDO:0013896, Orofaciodigital syndrome IV, MIM# 258860, Mohr-Majewski syndrome, Meckel-Gruber syndrome
Mendeliome v0.8217 SDCCAG8 Zornitza Stark Marked gene: SDCCAG8 as ready
Mendeliome v0.8217 SDCCAG8 Zornitza Stark Gene: sdccag8 has been classified as Green List (High Evidence).
Mendeliome v0.8217 SDCCAG8 Zornitza Stark Phenotypes for gene: SDCCAG8 were changed from to Bardet-Biedl syndrome 16, MIM# 615993; MONDO:0014444; Senior-Loken syndrome 7, MIM# 613615; MONDO:0013326; Nephronophthisis
Mendeliome v0.8216 SDCCAG8 Zornitza Stark Publications for gene: SDCCAG8 were set to
Mendeliome v0.8215 SDCCAG8 Zornitza Stark Mode of inheritance for gene: SDCCAG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8214 SDCCAG8 Zornitza Stark reviewed gene: SDCCAG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 20835237, 22626039, 22626039, 32432520, 31534065, 26968886; Phenotypes: Bardet-Biedl syndrome 16, MIM# 615993, MONDO:0014444, Senior-Loken syndrome 7, MIM# 613615, MONDO:0013326, Nephronophthisis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8214 SBDS Zornitza Stark Marked gene: SBDS as ready
Mendeliome v0.8214 SBDS Zornitza Stark Gene: sbds has been classified as Green List (High Evidence).
Mendeliome v0.8214 SBDS Zornitza Stark Phenotypes for gene: SBDS were changed from to Shwachman-Diamond syndrome, MIM# 260400
Mendeliome v0.8213 SBDS Zornitza Stark Mode of inheritance for gene: SBDS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8212 SBDS Zornitza Stark reviewed gene: SBDS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Shwachman-Diamond syndrome, MIM# 260400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8212 RPGRIP1L Zornitza Stark Deleted their comment
Mendeliome v0.8212 RPGRIP1L Zornitza Stark Marked gene: RPGRIP1L as ready
Mendeliome v0.8212 RPGRIP1L Zornitza Stark Gene: rpgrip1l has been classified as Green List (High Evidence).
Mendeliome v0.8212 RPGRIP1L Zornitza Stark Phenotypes for gene: RPGRIP1L were changed from to Joubert syndrome 7, MIM# 611560; Meckel syndrome 5, MIM# 611561; COACH syndrome 3, MIM# 619113; Nephronophthisis
Mendeliome v0.8211 RPGRIP1L Zornitza Stark Publications for gene: RPGRIP1L were set to
Mendeliome v0.8210 RPGRIP1L Zornitza Stark Mode of inheritance for gene: RPGRIP1L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8209 RPGRIP1L Zornitza Stark edited their review of gene: RPGRIP1L: Added comment: Bi-allelic variants in this gene are associated with a range of ciliopathies, including JBTS and Meckel syndrome. Mouse model.; Changed publications: 17558409, 17558407, 17960139, 26071364, 19574260, 29991045; Changed phenotypes: Joubert syndrome 7, MIM# 611560, Meckel syndrome 5, MIM# 611561, COACH syndrome 3, MIM# 619113, Nephronophthisis
Mendeliome v0.8209 NPHP4 Zornitza Stark Marked gene: NPHP4 as ready
Mendeliome v0.8209 NPHP4 Zornitza Stark Gene: nphp4 has been classified as Green List (High Evidence).
Mendeliome v0.8209 NPHP4 Zornitza Stark Phenotypes for gene: NPHP4 were changed from to Nephronophthisis 4, MIM# 606966; Senior-Loken syndrome 4, MIM# 606996
Mendeliome v0.8208 NPHP4 Zornitza Stark Publications for gene: NPHP4 were set to
Mendeliome v0.8207 NPHP4 Zornitza Stark Mode of inheritance for gene: NPHP4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8206 NPHP4 Zornitza Stark reviewed gene: NPHP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12244321, 12205563, 34013113; Phenotypes: Nephronophthisis 4, MIM# 606966, Senior-Loken syndrome 4, MIM# 606996; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8206 NPHP1 Zornitza Stark Marked gene: NPHP1 as ready
Mendeliome v0.8206 NPHP1 Zornitza Stark Gene: nphp1 has been classified as Green List (High Evidence).
Mendeliome v0.8206 NPHP1 Zornitza Stark Phenotypes for gene: NPHP1 were changed from to Joubert syndrome 4, MIM# 609583; Nephronophthisis 1, juvenile, MIM# 256100; Senior-Loken syndrome-1, MIM# 266900
Mendeliome v0.8205 NPHP1 Zornitza Stark Publications for gene: NPHP1 were set to
Mendeliome v0.8204 NPHP1 Zornitza Stark Mode of inheritance for gene: NPHP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8203 NPHP1 Zornitza Stark Tag SV/CNV tag was added to gene: NPHP1.
Mendeliome v0.8203 NPHP1 Zornitza Stark reviewed gene: NPHP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15138899, 32139166, 28347285, 8852662, 9856524; Phenotypes: Joubert syndrome 4, MIM# 609583, Nephronophthisis 1, juvenile, MIM# 256100, Senior-Loken syndrome-1, MIM# 266900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8203 TIE1 Zornitza Stark Marked gene: TIE1 as ready
Mendeliome v0.8203 TIE1 Zornitza Stark Gene: tie1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8203 TIE1 Zornitza Stark Classified gene: TIE1 as Amber List (moderate evidence)
Mendeliome v0.8203 TIE1 Zornitza Stark Gene: tie1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8202 TIE1 Zornitza Stark gene: TIE1 was added
gene: TIE1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TIE1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TIE1 were set to 32947856; 24764452
Phenotypes for gene: TIE1 were set to Lymphatic malformation 11, MIM# 619401
Review for gene: TIE1 was set to AMBER
Added comment: Three families reported, supportive animal model, though variants are missense and present at a low frequency in gnomad.
Sources: Literature
Mendeliome v0.8201 KIF1B Paul De Fazio reviewed gene: KIF1B: Rating: RED; Mode of pathogenicity: None; Publications: 33710394; Phenotypes: Hypotonia, coloboma, hypoplasia of the corpus callosum, severe neurodevelopmental delay; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.8201 NUF2 Dean Phelan gene: NUF2 was added
gene: NUF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NUF2 were set to PMID: 33721060
Phenotypes for gene: NUF2 were set to microcephaly; short stature; bilateral vocal cord paralysis; micrognathia; atrial septal defect
Review for gene: NUF2 was set to RED
Added comment: PMID: 33721060 - de novo missense variant identified in one male patient with microcephaly and short stature, with additional features, such as bilateral vocal cord paralysis, micrognathia and atrial septal defect.
Sources: Literature
Mendeliome v0.8201 ERGIC3 Elena Savva gene: ERGIC3 was added
gene: ERGIC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ERGIC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERGIC3 were set to PMID: 33710394; 31585110
Phenotypes for gene: ERGIC3 were set to Intellectual disability
Review for gene: ERGIC3 was set to AMBER
Added comment: PMID: 33710394 - two homozygous sibs with mild ID, a novel canonical splice (c.717+1G>A). Absent in gnomAD, no splice studies. Classed as a VUS.

PMID: 31585110 - 1 hom (p.Gln233Argfs*10) in a male 8yo with Growth retardation, Microcephaly, Learning disability, Facial dysmorphism, Abnormal pigmentation.
Sources: Literature
Mendeliome v0.8201 JPH3 Teresa Zhao reviewed gene: JPH3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 33824468; Phenotypes: Huntington disease-like 2 (MIM#606438) AD; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8201 HEATR5B Teresa Zhao gene: HEATR5B was added
gene: HEATR5B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HEATR5B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEATR5B were set to PMID: 33824466
Phenotypes for gene: HEATR5B were set to pontocerebellar hypoplasia
Review for gene: HEATR5B was set to AMBER
Added comment: Four affected children from two families presenting with pontocerebellar hypoplasiawith neonatal seizures, severe ID and motor delay.

Two homozygous splice variants were reported ((c.5051–1G>A and c.5050+4A>G) in intron 31 of HEATR5B gene. Aberrant splicing was found in patient fibroblasts, which correlated
with reduced levels of HEATR5B protein.

Homozygous knockout mice were not viable.

*NOTE: gene (and alias) not found in OMIM
Sources: Literature
Mendeliome v0.8201 NEK8 Zornitza Stark Marked gene: NEK8 as ready
Mendeliome v0.8201 NEK8 Zornitza Stark Gene: nek8 has been classified as Green List (High Evidence).
Mendeliome v0.8201 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from to Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174
Mendeliome v0.8200 NEK8 Zornitza Stark Publications for gene: NEK8 were set to
Mendeliome v0.8199 NEK8 Zornitza Stark Mode of inheritance for gene: NEK8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8198 NEK8 Zornitza Stark reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: None; Publications: 33131162, 23418306, 26862157, 26697755, 26967905, 23274954, 31633649; Phenotypes: Renal-hepatic-pancreatic dysplasia 2, MIM# 615415, MONDO:0014174; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8198 MKKS Zornitza Stark Marked gene: MKKS as ready
Mendeliome v0.8198 MKKS Zornitza Stark Gene: mkks has been classified as Green List (High Evidence).
Mendeliome v0.8198 MKKS Zornitza Stark Phenotypes for gene: MKKS were changed from to Bardet-Biedl syndrome 6 (MIM#605231); McKusick-Kaufman syndrome, MIM# 236700; Retinitis pigmentosa
Mendeliome v0.8197 MKKS Zornitza Stark Publications for gene: MKKS were set to
Mendeliome v0.8196 MKKS Zornitza Stark Mode of inheritance for gene: MKKS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8195 MKKS Zornitza Stark reviewed gene: MKKS: Rating: GREEN; Mode of pathogenicity: None; Publications: 10802661, 26900326, 10973251; Phenotypes: Bardet-Biedl syndrome 6 (MIM#605231), McKusick-Kaufman syndrome, MIM# 236700, Retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8195 IQCB1 Zornitza Stark Marked gene: IQCB1 as ready
Mendeliome v0.8195 IQCB1 Zornitza Stark Gene: iqcb1 has been classified as Green List (High Evidence).
Mendeliome v0.8195 IQCB1 Zornitza Stark Phenotypes for gene: IQCB1 were changed from to Senior-Loken syndrome 5, MIM# 609254; MONDO:0012225
Mendeliome v0.8194 IQCB1 Zornitza Stark Publications for gene: IQCB1 were set to
Mendeliome v0.8193 IQCB1 Zornitza Stark Mode of inheritance for gene: IQCB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8192 IQCB1 Zornitza Stark reviewed gene: IQCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15723066, 21220633, 20881296, 21901789, 33512896, 33535056, 29219953; Phenotypes: Senior-Loken syndrome 5, MIM# 609254, MONDO:0012225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8192 IFT80 Zornitza Stark Marked gene: IFT80 as ready
Mendeliome v0.8192 IFT80 Zornitza Stark Gene: ift80 has been classified as Green List (High Evidence).
Mendeliome v0.8192 IFT80 Zornitza Stark Phenotypes for gene: IFT80 were changed from to Short-rib thoracic dysplasia 2 with or without polydactyly, MIM# 611263; MONDO:0012644
Mendeliome v0.8191 IFT80 Zornitza Stark Publications for gene: IFT80 were set to
Mendeliome v0.8190 IFT80 Zornitza Stark Mode of inheritance for gene: IFT80 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8189 IFT80 Zornitza Stark commented on gene: IFT80: 5 unrelated families reported.
Mendeliome v0.8189 IFT80 Zornitza Stark reviewed gene: IFT80: Rating: GREEN; Mode of pathogenicity: None; Publications: 17468754, 19648123, 30767363; Phenotypes: Short-rib thoracic dysplasia 2 with or without polydactyly, MIM# 611263, MONDO:0012644; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8189 LZTFL1 Zornitza Stark Marked gene: LZTFL1 as ready
Mendeliome v0.8189 LZTFL1 Zornitza Stark Gene: lztfl1 has been classified as Green List (High Evidence).
Mendeliome v0.8189 LZTFL1 Zornitza Stark Phenotypes for gene: LZTFL1 were changed from to Bardet-Biedl syndrome 17 (MIM#615994)
Mendeliome v0.8188 LZTFL1 Zornitza Stark Publications for gene: LZTFL1 were set to
Mendeliome v0.8187 LZTFL1 Zornitza Stark Mode of inheritance for gene: LZTFL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8186 LZTFL1 Zornitza Stark reviewed gene: LZTFL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22510444, 23692385, 27312011, 22072986; Phenotypes: Bardet-Biedl syndrome 17 (MIM#615994); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8186 TTC26 Zornitza Stark changed review comment from: Seven families and functional data including zebrafish model.
Sources: Literature; to: Nine families and functional data including zebrafish model.
Sources: Literature
Mendeliome v0.8186 TTC26 Zornitza Stark changed review comment from: Three unrelated families and functional data including zebrafish model.
Sources: Literature; to: Seven families and functional data including zebrafish model.
Sources: Literature
Mendeliome v0.8186 TTC26 Zornitza Stark Marked gene: TTC26 as ready
Mendeliome v0.8186 TTC26 Zornitza Stark Gene: ttc26 has been classified as Green List (High Evidence).
Mendeliome v0.8186 TTC26 Zornitza Stark Classified gene: TTC26 as Green List (high evidence)
Mendeliome v0.8186 TTC26 Zornitza Stark Gene: ttc26 has been classified as Green List (High Evidence).
Mendeliome v0.8185 TTC26 Zornitza Stark gene: TTC26 was added
gene: TTC26 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TTC26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC26 were set to 34177428; 32617964; 31595528; 24596149; 22718903
Phenotypes for gene: TTC26 were set to Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations
Review for gene: TTC26 was set to GREEN
Added comment: Three unrelated families and functional data including zebrafish model.
Sources: Literature
Mendeliome v0.8184 IFT43 Zornitza Stark Publications for gene: IFT43 were set to 28400947; 28973684; 21378380
Mendeliome v0.8183 IFT43 Zornitza Stark changed review comment from: One family reported with cranioectodermal dysplasia, one with RP, and two with skeletal ciliopathy.; to: Two families reported with cranioectodermal dysplasia, one with RP, and two with skeletal ciliopathy.
Mendeliome v0.8183 IFT43 Zornitza Stark edited their review of gene: IFT43: Changed publications: 28400947, 28973684, 21378380, 29896747
Mendeliome v0.8183 IFT43 Zornitza Stark Marked gene: IFT43 as ready
Mendeliome v0.8183 IFT43 Zornitza Stark Gene: ift43 has been classified as Green List (High Evidence).
Mendeliome v0.8183 IFT43 Zornitza Stark Phenotypes for gene: IFT43 were changed from to Short-rib thoracic dysplasia 18 with polydactyly, MIM# 617866; Retinitis pigmentosa 81 , MIM#617871; Cranioectodermal dysplasia 3, MIM# 614099
Mendeliome v0.8182 IFT43 Zornitza Stark Publications for gene: IFT43 were set to
Mendeliome v0.8181 IFT43 Zornitza Stark Mode of inheritance for gene: IFT43 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8180 IFT43 Zornitza Stark reviewed gene: IFT43: Rating: GREEN; Mode of pathogenicity: None; Publications: 28400947, 28973684, 21378380; Phenotypes: Short-rib thoracic dysplasia 18 with polydactyly, MIM# 617866, Retinitis pigmentosa 81 , MIM#617871, Cranioectodermal dysplasia 3, MIM# 614099; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8180 IFT140 Zornitza Stark Marked gene: IFT140 as ready
Mendeliome v0.8180 IFT140 Zornitza Stark Gene: ift140 has been classified as Green List (High Evidence).
Mendeliome v0.8180 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from to Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; Retinitis pigmentosa 80, MIM# 617781
Mendeliome v0.8179 IFT140 Zornitza Stark Publications for gene: IFT140 were set to
Mendeliome v0.8178 IFT140 Zornitza Stark Mode of inheritance for gene: IFT140 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8177 IFT140 Zornitza Stark reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: 22503633, 23418020, 28288023, 28724397, 26216056, 26968735; Phenotypes: Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920, Retinitis pigmentosa 80, MIM# 617781; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8177 ARHGEF9 Zornitza Stark Mode of inheritance for gene: ARHGEF9 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.8176 SNORA31 Zornitza Stark Phenotypes for gene: SNORA31 were changed from Susceptibility to HSV1 encephalitis to {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1}, MIM# 619396
Mendeliome v0.8175 SNORA31 Zornitza Stark edited their review of gene: SNORA31: Changed phenotypes: {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1}, MIM# 619396
Mendeliome v0.8175 DYNC2H1 Zornitza Stark Marked gene: DYNC2H1 as ready
Mendeliome v0.8175 DYNC2H1 Zornitza Stark Gene: dync2h1 has been classified as Green List (High Evidence).
Mendeliome v0.8175 DYNC2H1 Zornitza Stark Phenotypes for gene: DYNC2H1 were changed from to Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091; MONDO:0013127
Mendeliome v0.8174 DYNC2H1 Zornitza Stark Publications for gene: DYNC2H1 were set to
Mendeliome v0.8173 DYNC2H1 Zornitza Stark Mode of inheritance for gene: DYNC2H1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8172 DYNC2H1 Zornitza Stark reviewed gene: DYNC2H1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19442771, 19361615, 22499340, 23456818, 27925158; Phenotypes: Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091, MONDO:0013127; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8172 DDX59 Zornitza Stark Marked gene: DDX59 as ready
Mendeliome v0.8172 DDX59 Zornitza Stark Gene: ddx59 has been classified as Green List (High Evidence).
Mendeliome v0.8172 DDX59 Zornitza Stark Phenotypes for gene: DDX59 were changed from to Orofaciodigital syndrome V (MIM#174300)
Mendeliome v0.8171 DDX59 Zornitza Stark Publications for gene: DDX59 were set to
Mendeliome v0.8170 DDX59 Zornitza Stark Mode of inheritance for gene: DDX59 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8169 DDX59 Zornitza Stark reviewed gene: DDX59: Rating: GREEN; Mode of pathogenicity: None; Publications: 29127725, 23972372, 28711741; Phenotypes: Orofaciodigital syndrome V (MIM#174300); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8169 CEP83 Zornitza Stark Marked gene: CEP83 as ready
Mendeliome v0.8169 CEP83 Zornitza Stark Gene: cep83 has been classified as Green List (High Evidence).
Mendeliome v0.8169 CEP83 Zornitza Stark Phenotypes for gene: CEP83 were changed from to Nephronophthisis 18, MIM# 615862; MONDO:0014374; Retinal dystrophy; ID
Mendeliome v0.8168 CEP83 Zornitza Stark Publications for gene: CEP83 were set to
Mendeliome v0.8167 CEP83 Zornitza Stark Mode of inheritance for gene: CEP83 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8166 CEP83 Zornitza Stark reviewed gene: CEP83: Rating: GREEN; Mode of pathogenicity: None; Publications: 24882706, 33938610; Phenotypes: Nephronophthisis 18, MIM# 615862, MONDO:0014374, Retinal dystrophy, ID; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8166 RNU12 Bryony Thompson Marked gene: RNU12 as ready
Mendeliome v0.8166 RNU12 Bryony Thompson Gene: rnu12 has been classified as Green List (High Evidence).
Mendeliome v0.8166 RNU12 Bryony Thompson Classified gene: RNU12 as Green List (high evidence)
Mendeliome v0.8166 RNU12 Bryony Thompson Gene: rnu12 has been classified as Green List (High Evidence).
Mendeliome v0.8165 RNU12 Bryony Thompson gene: RNU12 was added
gene: RNU12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNU12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU12 were set to 34085356; 27863452
Phenotypes for gene: RNU12 were set to CDAGS syndrome MIM#603116; Craniosynostosis, Delayed closure of the fontanelles, cranial defects, clavicular hypoplasia, Anal and Genitourinary malformations, and Skin manifestations
Review for gene: RNU12 was set to GREEN
Added comment: 5 CDAGS syndrome families with biallelic variants all including NC_000022.10:g.43011402C>T and another variant on the second allele. Whole transcriptome sequencing analysis of patient lymphoblastoid cells identified differentially expressed genes, and differential alternative splicing analysis indicated there was an enrichment of alternative splicing events. Also, limited evidence for an association with cerebellar ataxia with a single large consanguineous family reported with a homozygous variant.
Sources: Literature
Mendeliome v0.8164 FHOD3 Zornitza Stark Marked gene: FHOD3 as ready
Mendeliome v0.8164 FHOD3 Zornitza Stark Gene: fhod3 has been classified as Green List (High Evidence).
Mendeliome v0.8164 FHOD3 Zornitza Stark Phenotypes for gene: FHOD3 were changed from to Cardiomyopathy, familial hypertrophic, 28, MIM# 619402
Mendeliome v0.8163 FHOD3 Zornitza Stark Publications for gene: FHOD3 were set to
Mendeliome v0.8162 FHOD3 Zornitza Stark Mode of inheritance for gene: FHOD3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8161 FHOD3 Zornitza Stark Tag SV/CNV tag was added to gene: FHOD3.
Mendeliome v0.8161 FHOD3 Zornitza Stark reviewed gene: FHOD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32335906, 31742804, 30442288; Phenotypes: Cardiomyopathy, familial hypertrophic, 28, MIM# 619402; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8161 PPP1R21 Zornitza Stark Phenotypes for gene: PPP1R21 were changed from Hypotonia; intellectual disability; white matter abnormalities to Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities, MIM# 619383; Hypotonia; intellectual disability; white matter abnormalities
Mendeliome v0.8160 PPP1R21 Zornitza Stark edited their review of gene: PPP1R21: Changed phenotypes: Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities, MIM# 619383, Hypotonia, intellectual disability, white matter abnormalities
Mendeliome v0.8160 KCNJ16 Zornitza Stark Marked gene: KCNJ16 as ready
Mendeliome v0.8160 KCNJ16 Zornitza Stark Gene: kcnj16 has been classified as Green List (High Evidence).
Mendeliome v0.8160 KCNJ16 Zornitza Stark Classified gene: KCNJ16 as Green List (high evidence)
Mendeliome v0.8160 KCNJ16 Zornitza Stark Gene: kcnj16 has been classified as Green List (High Evidence).
Mendeliome v0.8159 KCNJ16 Zornitza Stark gene: KCNJ16 was added
gene: KCNJ16 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCNJ16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KCNJ16 were set to 33811157; 33840812
Phenotypes for gene: KCNJ16 were set to Renal tubulopathy; deafness
Review for gene: KCNJ16 was set to GREEN
Added comment: 8 unrelated families reported.
Sources: Literature
Mendeliome v0.8158 KLHL7 Zornitza Stark Marked gene: KLHL7 as ready
Mendeliome v0.8158 KLHL7 Zornitza Stark Gene: klhl7 has been classified as Green List (High Evidence).
Mendeliome v0.8158 KLHL7 Zornitza Stark Phenotypes for gene: KLHL7 were changed from to PERCHING syndrome (MIM#617055); Retinitis pigmentosa 42 (MIM#612943)
Mendeliome v0.8157 KLHL7 Zornitza Stark Publications for gene: KLHL7 were set to
Mendeliome v0.8156 KLHL7 Zornitza Stark Mode of inheritance for gene: KLHL7 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.8155 SLC34A3 Zornitza Stark Marked gene: SLC34A3 as ready
Mendeliome v0.8155 SLC34A3 Zornitza Stark Gene: slc34a3 has been classified as Green List (High Evidence).
Mendeliome v0.8155 SLC34A3 Zornitza Stark Phenotypes for gene: SLC34A3 were changed from to Hypophosphatemic rickets with hypercalciuria, (MIM#241530)
Mendeliome v0.8154 SLC34A3 Zornitza Stark Publications for gene: SLC34A3 were set to
Mendeliome v0.8153 SLC34A3 Zornitza Stark Mode of inheritance for gene: SLC34A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8152 TNC Zornitza Stark Marked gene: TNC as ready
Mendeliome v0.8152 TNC Zornitza Stark Gene: tnc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8152 TNC Zornitza Stark Phenotypes for gene: TNC were changed from to Deafness, autosomal dominant 56, MIM# 615629
Mendeliome v0.8151 TNC Zornitza Stark Publications for gene: TNC were set to
Mendeliome v0.8150 TNC Zornitza Stark Mode of inheritance for gene: TNC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8149 TNC Zornitza Stark Classified gene: TNC as Amber List (moderate evidence)
Mendeliome v0.8149 TNC Zornitza Stark Gene: tnc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8148 TNC Zornitza Stark reviewed gene: TNC: Rating: AMBER; Mode of pathogenicity: None; Publications: 23936043, 34093110, 33763067; Phenotypes: Deafness, autosomal dominant 56, MIM# 615629; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8148 RIPK4 Zornitza Stark Marked gene: RIPK4 as ready
Mendeliome v0.8148 RIPK4 Zornitza Stark Gene: ripk4 has been classified as Green List (High Evidence).
Mendeliome v0.8148 RIPK4 Zornitza Stark Phenotypes for gene: RIPK4 were changed from to Popliteal pterygium syndrome, Bartsocas-Papas type, MIM# 263650
Mendeliome v0.8147 RIPK4 Zornitza Stark Publications for gene: RIPK4 were set to
Mendeliome v0.8146 RIPK4 Zornitza Stark Mode of inheritance for gene: RIPK4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8145 RIPK4 Zornitza Stark reviewed gene: RIPK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28940926, 22197489, 22197488; Phenotypes: Popliteal pterygium syndrome, Bartsocas-Papas type, MIM# 263650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8145 KLHL7 Ain Roesley reviewed gene: KLHL7: Rating: GREEN; Mode of pathogenicity: None; Publications: 31953236, 30300710, 31856884; Phenotypes: PERCHING syndrome (MIM#617055), Retinitis pigmentosa 42 (MIM#612943); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.8145 SLC34A3 Ain Roesley reviewed gene: SLC34A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32524022; Phenotypes: Hypophosphatemic rickets with hypercalciuria, (MIM#241530); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8145 CEP290 Zornitza Stark Marked gene: CEP290 as ready
Mendeliome v0.8145 CEP290 Zornitza Stark Gene: cep290 has been classified as Green List (High Evidence).
Mendeliome v0.8145 CEP290 Zornitza Stark Phenotypes for gene: CEP290 were changed from to Bardet-Biedl syndrome 14, MIM# 615991; Joubert syndrome 5 610188; Leber congenital amaurosis 10, MIM# 611755; Meckel syndrome 4, MIM# 611134; Senior-Loken syndrome 6, MIM# 610189
Mendeliome v0.8144 CEP290 Zornitza Stark Publications for gene: CEP290 were set to
Mendeliome v0.8143 CEP290 Zornitza Stark Mode of inheritance for gene: CEP290 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8142 CEP290 Zornitza Stark reviewed gene: CEP290: Rating: GREEN; Mode of pathogenicity: None; Publications: 18327255, 20690115, 16682973, 16682970, 17564967, 16909394, 17564974; Phenotypes: Bardet-Biedl syndrome 14, MIM# 615991, Joubert syndrome 5 610188, Leber congenital amaurosis 10, MIM# 611755, Meckel syndrome 4, MIM# 611134, Senior-Loken syndrome 6, MIM# 610189; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8142 CEP164 Zornitza Stark Marked gene: CEP164 as ready
Mendeliome v0.8142 CEP164 Zornitza Stark Gene: cep164 has been classified as Green List (High Evidence).
Mendeliome v0.8142 CEP164 Zornitza Stark Phenotypes for gene: CEP164 were changed from to Bardet-Biedl syndrome; Nephronophthisis 15, MIM# 614845; Oro-facio-digital syndrome
Mendeliome v0.8141 CEP164 Zornitza Stark Publications for gene: CEP164 were set to
Mendeliome v0.8140 CEP164 Zornitza Stark Mode of inheritance for gene: CEP164 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8139 CEP164 Zornitza Stark reviewed gene: CEP164: Rating: GREEN; Mode of pathogenicity: None; Publications: 34132027, 34013113, 32055034, 27708425, 22863007; Phenotypes: Bardet-Biedl syndrome, Nephronophthisis 15, MIM# 614845, Oro-facio-digital syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8139 CEP120 Zornitza Stark Marked gene: CEP120 as ready
Mendeliome v0.8139 CEP120 Zornitza Stark Gene: cep120 has been classified as Green List (High Evidence).
Mendeliome v0.8139 CEP120 Zornitza Stark Phenotypes for gene: CEP120 were changed from to Joubert syndrome 31, MIM# 617761; Short-rib thoracic dysplasia 13 with or without polydactyly, MIM# 616300
Mendeliome v0.8138 CEP120 Zornitza Stark Publications for gene: CEP120 were set to
Mendeliome v0.8137 CEP120 Zornitza Stark Mode of inheritance for gene: CEP120 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8136 CEP120 Zornitza Stark reviewed gene: CEP120: Rating: GREEN; Mode of pathogenicity: None; Publications: 27208211, 33486889, 29847808, 25361962, 27208211; Phenotypes: Joubert syndrome 31, MIM# 617761, Short-rib thoracic dysplasia 13 with or without polydactyly, MIM# 616300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8136 CEP104 Zornitza Stark Marked gene: CEP104 as ready
Mendeliome v0.8136 CEP104 Zornitza Stark Gene: cep104 has been classified as Green List (High Evidence).
Mendeliome v0.8136 CEP104 Zornitza Stark Phenotypes for gene: CEP104 were changed from to Joubert syndrome 25, MIM# 616781; MONDO:0014770
Mendeliome v0.8135 CEP104 Zornitza Stark Publications for gene: CEP104 were set to
Mendeliome v0.8134 CEP104 Zornitza Stark Mode of inheritance for gene: CEP104 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8133 CEP104 Zornitza Stark reviewed gene: CEP104: Rating: GREEN; Mode of pathogenicity: None; Publications: 26477546; Phenotypes: Joubert syndrome 25, MIM# 616781, MONDO:0014770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8133 C5orf42 Zornitza Stark Tag new gene name tag was added to gene: C5orf42.
Mendeliome v0.8133 C5orf42 Zornitza Stark Marked gene: C5orf42 as ready
Mendeliome v0.8133 C5orf42 Zornitza Stark Gene: c5orf42 has been classified as Green List (High Evidence).
Mendeliome v0.8133 C5orf42 Zornitza Stark Phenotypes for gene: C5orf42 were changed from to Joubert syndrome 17, MIM# 614615; Orofaciodigital syndrome VI, MIM# 277170
Mendeliome v0.8132 C5orf42 Zornitza Stark Publications for gene: C5orf42 were set to
Mendeliome v0.8131 C5orf42 Zornitza Stark Mode of inheritance for gene: C5orf42 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8130 C5orf42 Zornitza Stark changed review comment from: Well established gene-disease association.

New gene name is CPLANE1.; to: Well established gene-disease associations. More than 10 families reported with each association.

New gene name is CPLANE1.
Mendeliome v0.8130 C5orf42 Zornitza Stark Deleted their comment
Mendeliome v0.8130 C5orf42 Zornitza Stark edited their review of gene: C5orf42: Changed phenotypes: Joubert syndrome 17, MIM# 614615, Orofaciodigital syndrome VI, MIM# 277170
Mendeliome v0.8130 C5orf42 Zornitza Stark edited their review of gene: C5orf42: Changed publications: 22425360, 24178751
Mendeliome v0.8130 C5orf42 Zornitza Stark edited their review of gene: C5orf42: Added comment: Well established gene-disease association.

New gene name is CPLANE1.; Changed publications: 22425360
Mendeliome v0.8130 C21orf2 Zornitza Stark changed review comment from: Axial spondylometaphyseal dysplasia (SMDAX) is characterized by postnatal growth failure, including rhizomelic short stature in early childhood that evolves into short trunk in late childhood, and thoracic hypoplasia that may cause mild to moderate respiratory problems in the neonatal period and later susceptibility to airway infection. Impaired visual acuity comes to medical attention in early life and vision rapidly deteriorates. Retinal changes are diagnosed as retinitis pigmentosa or pigmentary retinal degeneration on funduscopic examination and as cone-rod dystrophy on ERG. Radiologic hallmarks include short ribs with flared and cupped anterior ends, mild spondylar dysplasia, lacy iliac crests, and metaphyseal irregularities essentially confined to the proximal femora. At least 7 unrelated families reported.

7 families also reported with isolated retinal dystrophy.; to: Axial spondylometaphyseal dysplasia (SMDAX) is characterized by postnatal growth failure, including rhizomelic short stature in early childhood that evolves into short trunk in late childhood, and thoracic hypoplasia that may cause mild to moderate respiratory problems in the neonatal period and later susceptibility to airway infection. Impaired visual acuity comes to medical attention in early life and vision rapidly deteriorates. Retinal changes are diagnosed as retinitis pigmentosa or pigmentary retinal degeneration on funduscopic examination and as cone-rod dystrophy on ERG. Radiologic hallmarks include short ribs with flared and cupped anterior ends, mild spondylar dysplasia, lacy iliac crests, and metaphyseal irregularities essentially confined to the proximal femora. At least 7 unrelated families reported.

7 families also reported with isolated retinal dystrophy.

New HGNC approved name is CFAP410.
Mendeliome v0.8130 C21orf2 Zornitza Stark Tag new gene name tag was added to gene: C21orf2.
Mendeliome v0.8130 C21orf2 Zornitza Stark Marked gene: C21orf2 as ready
Mendeliome v0.8130 C21orf2 Zornitza Stark Gene: c21orf2 has been classified as Green List (High Evidence).
Mendeliome v0.8130 C21orf2 Zornitza Stark Phenotypes for gene: C21orf2 were changed from to Spondylometaphyseal dysplasia, axial, MIM# 602271; Retinal dystrophy with macular staphyloma, MIM# 617547
Mendeliome v0.8129 C21orf2 Zornitza Stark Publications for gene: C21orf2 were set to
Mendeliome v0.8128 C21orf2 Zornitza Stark Mode of inheritance for gene: C21orf2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8127 C21orf2 Zornitza Stark reviewed gene: C21orf2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26974433, 27548899, 28422394, 26294103, 23105016, 27548899; Phenotypes: Spondylometaphyseal dysplasia, axial, MIM# 602271, Retinal dystrophy with macular staphyloma, MIM# 617547; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8127 BBS9 Zornitza Stark Marked gene: BBS9 as ready
Mendeliome v0.8127 BBS9 Zornitza Stark Gene: bbs9 has been classified as Green List (High Evidence).
Mendeliome v0.8127 BBS9 Zornitza Stark Phenotypes for gene: BBS9 were changed from to Bardet-Biedl syndrome 9, MIM#615986; MONDO:0014437
Mendeliome v0.8126 BBS9 Zornitza Stark Publications for gene: BBS9 were set to
Mendeliome v0.8125 BBS9 Zornitza Stark Mode of inheritance for gene: BBS9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8124 BBS9 Zornitza Stark reviewed gene: BBS9: Rating: GREEN; Mode of pathogenicity: None; Publications: 16380913, 22353939, 32686083, 32037757; Phenotypes: Bardet-Biedl syndrome 9, MIM#615986, MONDO:0014437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8124 BBS7 Zornitza Stark Marked gene: BBS7 as ready
Mendeliome v0.8124 BBS7 Zornitza Stark Gene: bbs7 has been classified as Green List (High Evidence).
Mendeliome v0.8124 BBS7 Zornitza Stark Phenotypes for gene: BBS7 were changed from to Bardet-Biedl syndrome 7, MIM# 615984; MONDO:0014435
Mendeliome v0.8123 BBS7 Zornitza Stark Publications for gene: BBS7 were set to
Mendeliome v0.8122 BBS7 Zornitza Stark Mode of inheritance for gene: BBS7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8121 BBS7 Zornitza Stark reviewed gene: BBS7: Rating: GREEN; Mode of pathogenicity: None; Publications: 12567324, 21937992, 19797195; Phenotypes: Bardet-Biedl syndrome 7, MIM# 615984, MONDO:0014435; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8121 BBS5 Zornitza Stark Marked gene: BBS5 as ready
Mendeliome v0.8121 BBS5 Zornitza Stark Gene: bbs5 has been classified as Green List (High Evidence).
Mendeliome v0.8121 BBS5 Zornitza Stark Phenotypes for gene: BBS5 were changed from to Bardet-Biedl syndrome 5, MIM#615983; MONDO:0014434
Mendeliome v0.8120 BBS5 Zornitza Stark Publications for gene: BBS5 were set to
Mendeliome v0.8119 BBS5 Zornitza Stark Mode of inheritance for gene: BBS5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8118 BBS5 Zornitza Stark reviewed gene: BBS5: Rating: GREEN; Mode of pathogenicity: None; Publications: 19252258, 15137946, 10053027, 15637713; Phenotypes: Bardet-Biedl syndrome 5, MIM#615983, MONDO:0014434; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8118 BBS4 Zornitza Stark Marked gene: BBS4 as ready
Mendeliome v0.8118 BBS4 Zornitza Stark Gene: bbs4 has been classified as Green List (High Evidence).
Mendeliome v0.8118 BBS4 Zornitza Stark Phenotypes for gene: BBS4 were changed from to Bardet-Biedl syndrome 4, MIM#615982; MONDO:0014433
Mendeliome v0.8117 BBS4 Zornitza Stark Publications for gene: BBS4 were set to
Mendeliome v0.8116 BBS4 Zornitza Stark Mode of inheritance for gene: BBS4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8115 BBS4 Zornitza Stark reviewed gene: BBS4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12016587, 11381270; Phenotypes: Bardet-Biedl syndrome 4, MIM#615982, MONDO:0014433; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8115 ARL6 Zornitza Stark Marked gene: ARL6 as ready
Mendeliome v0.8115 ARL6 Zornitza Stark Gene: arl6 has been classified as Green List (High Evidence).
Mendeliome v0.8115 ARL6 Zornitza Stark Phenotypes for gene: ARL6 were changed from to Bardet-Biedl syndrome 3, MIM# 600151; Retinitis pigmentosa 55, MIM# 613575
Mendeliome v0.8114 ARL6 Zornitza Stark Publications for gene: ARL6 were set to
Mendeliome v0.8113 ARL6 Zornitza Stark Mode of inheritance for gene: ARL6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8112 ARL6 Zornitza Stark reviewed gene: ARL6: Rating: GREEN; Mode of pathogenicity: None; Publications: 15258860, 32361989, 31888296, 25402481, 31736247, 19858128; Phenotypes: Bardet-Biedl syndrome 3, MIM# 600151, Retinitis pigmentosa 55, MIM# 613575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8112 IL37 Zornitza Stark Phenotypes for gene: IL37 were changed from Infantile inflammatory bowel disease to Inflammatory bowel disease (infantile ulcerative colitis) 31, MIM# 619398
Mendeliome v0.8111 IL37 Zornitza Stark edited their review of gene: IL37: Changed phenotypes: Inflammatory bowel disease (infantile ulcerative colitis) 31, MIM# 619398
Mendeliome v0.8111 SLCO2A1 Zornitza Stark Phenotypes for gene: SLCO2A1 were changed from to Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100; Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441
Mendeliome v0.8110 SLCO2A1 Zornitza Stark Publications for gene: SLCO2A1 were set to
Mendeliome v0.8109 SLCO2A1 Zornitza Stark Mode of inheritance for gene: SLCO2A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8108 SLCO2A1 Zornitza Stark edited their review of gene: SLCO2A1: Changed publications: 23509104, 27134495, 33852188, 22331663, 27134495
Mendeliome v0.8108 SLCO2A1 Zornitza Stark reviewed gene: SLCO2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23509104, 27134495, 33852188, 22331663, 27134495]; Phenotypes: Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100, Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8108 NDUFB11 Zornitza Stark edited their review of gene: NDUFB11: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8108 NDUFB11 Zornitza Stark Phenotypes for gene: NDUFB11 were changed from Linear skin defects with multiple congenital anomalies 3, XLD (MIM#300952); MONDO:0010494; Mitochondrial complex I deficiency, nuclear type 30, XLR (MIM#301021); MONDO:0026721 to Linear skin defects with multiple congenital anomalies 3, XLD (MIM#300952); MONDO:0010494; Mitochondrial complex I deficiency, nuclear type 30, XLR (MIM#301021); MONDO:0026721; X-linked sideroblastic anaemia
Mendeliome v0.8107 NDUFB11 Zornitza Stark Publications for gene: NDUFB11 were set to 28050600; 27488349; 30423443; 27488349
Mendeliome v0.8106 NDUFB11 Zornitza Stark reviewed gene: NDUFB11: Rating: GREEN; Mode of pathogenicity: None; Publications: 27488349; Phenotypes: X-linked sideroblastic anaemia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8106 PPP2R1A Zornitza Stark changed review comment from: Intellectual disability with variable other features, including CC abnormalities and microcephaly.; to: Intellectual disability with variable other features, including CC abnormalities and microcephaly/macrocephaly.
Mendeliome v0.8106 PPP2R1A Zornitza Stark Marked gene: PPP2R1A as ready
Mendeliome v0.8106 PPP2R1A Zornitza Stark Gene: ppp2r1a has been classified as Green List (High Evidence).
Mendeliome v0.8106 PPP2R1A Zornitza Stark Phenotypes for gene: PPP2R1A were changed from to Mental retardation, autosomal dominant 36, MIM#616362; Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome, MONDO:0014605
Mendeliome v0.8105 PPP2R1A Zornitza Stark Publications for gene: PPP2R1A were set to
Mendeliome v0.8104 PPP2R1A Zornitza Stark Mode of inheritance for gene: PPP2R1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8103 PPP2R1A Zornitza Stark reviewed gene: PPP2R1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal dominant 36, MIM#616362, Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome, MONDO:0014605; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8103 KIF1B Bryony Thompson Classified gene: KIF1B as Amber List (moderate evidence)
Mendeliome v0.8103 KIF1B Bryony Thompson Gene: kif1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8102 ARHGEF10 Bryony Thompson Marked gene: ARHGEF10 as ready
Mendeliome v0.8102 ARHGEF10 Bryony Thompson Gene: arhgef10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8102 ARHGEF10 Bryony Thompson Classified gene: ARHGEF10 as Amber List (moderate evidence)
Mendeliome v0.8102 ARHGEF10 Bryony Thompson Added comment: Comment on list classification: ClinGen gene-disease clinical validity classification is limited for this gene.
Mendeliome v0.8102 ARHGEF10 Bryony Thompson Gene: arhgef10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8100 PPP2R1A Elena Savva reviewed gene: PPP2R1A: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 26168268, 33106617; Phenotypes: Mental retardation, autosomal dominant 36 MIM#616362; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.8100 CLPB Zornitza Stark Marked gene: CLPB as ready
Mendeliome v0.8100 CLPB Zornitza Stark Gene: clpb has been classified as Green List (High Evidence).
Mendeliome v0.8100 CLPB Zornitza Stark Phenotypes for gene: CLPB were changed from to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271
Mendeliome v0.8099 CLPB Zornitza Stark Publications for gene: CLPB were set to
Mendeliome v0.8098 CLPB Zornitza Stark Mode of inheritance for gene: CLPB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8097 CLPB Zornitza Stark reviewed gene: CLPB: Rating: GREEN; Mode of pathogenicity: None; Publications: 25597510, 34140661; Phenotypes: 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8097 SYK Zornitza Stark Phenotypes for gene: SYK were changed from Immune dysregulation and systemic inflammation to Immunodeficiency-82 with systemic inflammation (IMD82) , MIM#619381
Mendeliome v0.8096 SYK Zornitza Stark reviewed gene: SYK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency-82 with systemic inflammation (IMD82) , MIM#619381; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8096 PON1 Zornitza Stark Marked gene: PON1 as ready
Mendeliome v0.8096 PON1 Zornitza Stark Gene: pon1 has been classified as Red List (Low Evidence).
Mendeliome v0.8096 PON1 Zornitza Stark Phenotypes for gene: PON1 were changed from to {Coronary artery disease, susceptibility to}
Mendeliome v0.8095 PON1 Zornitza Stark Classified gene: PON1 as Red List (low evidence)
Mendeliome v0.8095 PON1 Zornitza Stark Gene: pon1 has been classified as Red List (Low Evidence).
Mendeliome v0.8094 PON1 Zornitza Stark reviewed gene: PON1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Coronary artery disease, susceptibility to}; Mode of inheritance: None
Mendeliome v0.8094 ABCB4 Zornitza Stark Marked gene: ABCB4 as ready
Mendeliome v0.8094 ABCB4 Zornitza Stark Gene: abcb4 has been classified as Green List (High Evidence).
Mendeliome v0.8094 ABCB4 Zornitza Stark Phenotypes for gene: ABCB4 were changed from to Cholestasis, progressive familial intrahepatic 3 MIM#602347; disorder of bile acid metabolism
Mendeliome v0.8093 ABCB4 Zornitza Stark Publications for gene: ABCB4 were set to
Mendeliome v0.8092 ABCB4 Zornitza Stark Mode of inheritance for gene: ABCB4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8091 OAS1 Zornitza Stark Marked gene: OAS1 as ready
Mendeliome v0.8091 OAS1 Zornitza Stark Gene: oas1 has been classified as Green List (High Evidence).
Mendeliome v0.8091 OAS1 Zornitza Stark Phenotypes for gene: OAS1 were changed from to Autoinflammatory immunodeficiency; infantile-onset pulmonary alveolar proteinosis; hypogammaglobulinaemia
Mendeliome v0.8090 OAS1 Zornitza Stark Publications for gene: OAS1 were set to
Mendeliome v0.8089 OAS1 Zornitza Stark Mode of pathogenicity for gene: OAS1 was changed from to Other
Mendeliome v0.8088 OAS1 Zornitza Stark Mode of inheritance for gene: OAS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8087 OAS1 Zornitza Stark reviewed gene: OAS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34145065, 29455859; Phenotypes: Autoinflammatory immunodeficiency, infantile-onset pulmonary alveolar proteinosis, hypogammaglobulinaemia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8087 SLIT3 Zornitza Stark Marked gene: SLIT3 as ready
Mendeliome v0.8087 SLIT3 Zornitza Stark Gene: slit3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8087 SLIT3 Zornitza Stark Classified gene: SLIT3 as Amber List (moderate evidence)
Mendeliome v0.8087 SLIT3 Zornitza Stark Gene: slit3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8086 SLIT3 Zornitza Stark gene: SLIT3 was added
gene: SLIT3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLIT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLIT3 were set to 33933663
Phenotypes for gene: SLIT3 were set to Congenital diaphragmatic hernia
Review for gene: SLIT3 was set to AMBER
Added comment: Two affected individuals, single family, supportive mouse model.
Sources: Literature
Mendeliome v0.8085 SOCS1 Zornitza Stark Phenotypes for gene: SOCS1 were changed from Common variable immunodeficiency; Early-onset autoimmunity to Autoinflammatory syndrome, familial, with or without immunodeficiency, MIM# 619375; Common variable immunodeficiency; Early-onset autoimmunity
Mendeliome v0.8084 SOCS1 Zornitza Stark edited their review of gene: SOCS1: Changed phenotypes: Autoinflammatory syndrome, familial, with or without immunodeficiency, MIM# 619375, Early-onset autoimmunity
Mendeliome v0.8084 LCP2 Zornitza Stark Phenotypes for gene: LCP2 were changed from Severe combined immunodeficiency to Immunodeficiency 81, MIM# 619374; Severe combined immunodeficiency
Mendeliome v0.8083 LCP2 Zornitza Stark edited their review of gene: LCP2: Changed phenotypes: Immunodeficiency 81, MIM# 619374, Severe combined immunodeficiency
Mendeliome v0.8083 IQGAP3 Zornitza Stark Marked gene: IQGAP3 as ready
Mendeliome v0.8083 IQGAP3 Zornitza Stark Gene: iqgap3 has been classified as Red List (Low Evidence).
Mendeliome v0.8083 IQGAP3 Zornitza Stark gene: IQGAP3 was added
gene: IQGAP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IQGAP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: IQGAP3 were set to Hereditary neuropathy
Review for gene: IQGAP3 was set to RED
Added comment: Single multiplex family, intronic variant, limited functional data.
Sources: Literature
Mendeliome v0.8082 TINF2 Zornitza Stark Marked gene: TINF2 as ready
Mendeliome v0.8082 TINF2 Zornitza Stark Gene: tinf2 has been classified as Green List (High Evidence).
Mendeliome v0.8082 TINF2 Zornitza Stark Phenotypes for gene: TINF2 were changed from to Dyskeratosis congenita, autosomal dominant 3, MIM# 613990; Revesz syndrome, MIM# 268130
Mendeliome v0.8081 TINF2 Zornitza Stark Publications for gene: TINF2 were set to
Mendeliome v0.8080 TINF2 Zornitza Stark Mode of inheritance for gene: TINF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8079 TINF2 Zornitza Stark edited their review of gene: TINF2: Added comment: RS is a severe variant of DKC with early bone marrow failure and retinopathy. Well established gene-disease associations.; Changed publications: 18252230, 21477109, 18979121, 18669893, 21199492, 33097095; Changed phenotypes: Dyskeratosis congenita, autosomal dominant 3, MIM# 613990, Revesz syndrome, MIM# 268130
Mendeliome v0.8079 POPDC3 Zornitza Stark changed review comment from: 5 affected individuals from 3 unrelated families reported, supportive animal model data.
Sources: Literature; to: 5 affected individuals from 3 unrelated families reported, supportive animal model data. Presentation was between adolescence and 40s with proximal muscle weakness primarily affecting the lower limbs, resulting in increased falls and difficulty running. The disorder was slowly progressive, with later involvement of the upper limbs. MRI showed fatty replacement of the thigh muscles and medial gastrocnemius, with some paraspinal muscles also affected. Some patients had calf hypertrophy. Serum CK was markedly elevated.
Sources: Literature
Mendeliome v0.8079 POPDC3 Zornitza Stark Marked gene: POPDC3 as ready
Mendeliome v0.8079 POPDC3 Zornitza Stark Gene: popdc3 has been classified as Green List (High Evidence).
Mendeliome v0.8079 POPDC3 Zornitza Stark Classified gene: POPDC3 as Green List (high evidence)
Mendeliome v0.8079 POPDC3 Zornitza Stark Gene: popdc3 has been classified as Green List (High Evidence).
Mendeliome v0.8078 POPDC3 Zornitza Stark gene: POPDC3 was added
gene: POPDC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POPDC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POPDC3 were set to 31610034
Phenotypes for gene: POPDC3 were set to Muscular dystrophy, limb-girdle, autosomal recessive 26, MIM# 618848
Review for gene: POPDC3 was set to GREEN
Added comment: 5 affected individuals from 3 unrelated families reported, supportive animal model data.
Sources: Literature
Mendeliome v0.8077 ACD Zornitza Stark Marked gene: ACD as ready
Mendeliome v0.8077 ACD Zornitza Stark Gene: acd has been classified as Red List (Low Evidence).
Mendeliome v0.8077 ACD Zornitza Stark Phenotypes for gene: ACD were changed from to Dyskeratosis congenita, MIM# 616553
Mendeliome v0.8076 ACD Zornitza Stark Publications for gene: ACD were set to
Mendeliome v0.8075 ACD Zornitza Stark Mode of inheritance for gene: ACD was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8074 ACD Zornitza Stark Classified gene: ACD as Red List (low evidence)
Mendeliome v0.8074 ACD Zornitza Stark Gene: acd has been classified as Red List (Low Evidence).
Mendeliome v0.8073 ACD Zornitza Stark reviewed gene: ACD: Rating: RED; Mode of pathogenicity: None; Publications: 25205116, 25233904; Phenotypes: Dyskeratosis congenita, MIM# 616553; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8073 USB1 Zornitza Stark Phenotypes for gene: USB1 were changed from Poikiloderma with neutropenia (OMIM #604173) to Poikiloderma with neutropaenia, MIM# 604173; MONDO:0011405
Mendeliome v0.8072 USB1 Zornitza Stark Publications for gene: USB1 were set to 25044170; 27612988
Mendeliome v0.8071 USB1 Zornitza Stark reviewed gene: USB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20004881, 20503306, 34004352, 33624217, 33111394, 32936385, 32620997, 31522452; Phenotypes: Poikiloderma with neutropaenia, MIM# 604173, MONDO:0011405; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8071 WRAP53 Zornitza Stark Marked gene: WRAP53 as ready
Mendeliome v0.8071 WRAP53 Zornitza Stark Gene: wrap53 has been classified as Green List (High Evidence).
Mendeliome v0.8071 WRAP53 Zornitza Stark Phenotypes for gene: WRAP53 were changed from to Dyskeratosis congenita, autosomal recessive 3, MIM# 613988
Mendeliome v0.8070 WRAP53 Zornitza Stark Publications for gene: WRAP53 were set to
Mendeliome v0.8069 WRAP53 Zornitza Stark Mode of inheritance for gene: WRAP53 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8069 WRAP53 Zornitza Stark Mode of inheritance for gene: WRAP53 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8068 WRAP53 Zornitza Stark reviewed gene: WRAP53: Rating: GREEN; Mode of pathogenicity: None; Publications: 21205863, 32303682, 29514627; Phenotypes: Dyskeratosis congenita, autosomal recessive 3, MIM# 613988; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8068 EP300 Zornitza Stark Marked gene: EP300 as ready
Mendeliome v0.8068 EP300 Zornitza Stark Gene: ep300 has been classified as Green List (High Evidence).
Mendeliome v0.8068 EP300 Zornitza Stark Phenotypes for gene: EP300 were changed from to Rubinstein-Taybi syndrome 2 MIM#613684; Menke-Hennekam syndrome 2 MIM#618333
Mendeliome v0.8067 EP300 Zornitza Stark Publications for gene: EP300 were set to
Mendeliome v0.8066 EP300 Zornitza Stark Mode of inheritance for gene: EP300 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8065 EP300 Elena Savva reviewed gene: EP300: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29460469, 24381114; Phenotypes: Rubinstein-Taybi syndrome 2 MIM#613684, Menke-Hennekam syndrome 2 MIM#618333, Colorectal cancer, somatic MIM#114500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.8065 PARN Zornitza Stark Marked gene: PARN as ready
Mendeliome v0.8065 PARN Zornitza Stark Gene: parn has been classified as Green List (High Evidence).
Mendeliome v0.8065 PARN Zornitza Stark Phenotypes for gene: PARN were changed from to Dyskeratosis congenita, autosomal recessive 6, MIM# 616353; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 4, MIM# 616371
Mendeliome v0.8064 PARN Zornitza Stark Publications for gene: PARN were set to
Mendeliome v0.8063 PARN Zornitza Stark Mode of inheritance for gene: PARN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8062 PARN Zornitza Stark reviewed gene: PARN: Rating: GREEN; Mode of pathogenicity: None; Publications: 25893599, 26342108, 25848748; Phenotypes: Dyskeratosis congenita, autosomal recessive 6, MIM# 616353, Pulmonary fibrosis and/or bone marrow failure, telomere-related, 4, MIM# 616371; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8062 KLF1 Zornitza Stark Marked gene: KLF1 as ready
Mendeliome v0.8062 KLF1 Zornitza Stark Gene: klf1 has been classified as Green List (High Evidence).
Mendeliome v0.8062 KLF1 Zornitza Stark Phenotypes for gene: KLF1 were changed from to Dyserythropoietic anaemia, congenital, type IV, MIM# 613673; MONDO:0013355
Mendeliome v0.8061 KLF1 Zornitza Stark Publications for gene: KLF1 were set to
Mendeliome v0.8060 KLF1 Zornitza Stark Mode of inheritance for gene: KLF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8059 KLF1 Zornitza Stark reviewed gene: KLF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21055716, 33339573, 32815883, 32221653, 32032242, 31818881; Phenotypes: Dyserythropoietic anaemia, congenital, type IV, MIM# 613673, MONDO:0013355; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8059 SPAG17 Zornitza Stark Marked gene: SPAG17 as ready
Mendeliome v0.8059 SPAG17 Zornitza Stark Gene: spag17 has been classified as Red List (Low Evidence).
Mendeliome v0.8059 SPAG17 Zornitza Stark gene: SPAG17 was added
gene: SPAG17 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPAG17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPAG17 were set to 28548327
Phenotypes for gene: SPAG17 were set to Spermatogenic failure 55, MIM#619380
Review for gene: SPAG17 was set to RED
Added comment: Single family reported with two affected brothers, homozygous missense variant.
Sources: Literature
Mendeliome v0.8058 CATIP Zornitza Stark Marked gene: CATIP as ready
Mendeliome v0.8058 CATIP Zornitza Stark Gene: catip has been classified as Red List (Low Evidence).
Mendeliome v0.8058 CATIP Zornitza Stark gene: CATIP was added
gene: CATIP was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CATIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CATIP were set to 32503832
Phenotypes for gene: CATIP were set to Spermatogenic failure 54, MIM# 619379
Review for gene: CATIP was set to RED
Added comment: Homozygous missense variant reported in a single consanguineous family with 4 affecteds. Limited functional data.
Sources: Expert list
Mendeliome v0.8057 NCDN Zornitza Stark Phenotypes for gene: NCDN were changed from neurodevelopmental delay, intellectual disability, and epilepsy to Neurodevelopmental disorder with infantile epileptic spasms (NEDIES), MIM#619373
Mendeliome v0.8056 NCDN Zornitza Stark reviewed gene: NCDN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with infantile epileptic spasms (NEDIES), MIM#619373; Mode of inheritance: None
Mendeliome v0.8056 HAX1 Zornitza Stark Marked gene: HAX1 as ready
Mendeliome v0.8056 HAX1 Zornitza Stark Gene: hax1 has been classified as Green List (High Evidence).
Mendeliome v0.8056 HAX1 Zornitza Stark Phenotypes for gene: HAX1 were changed from to Neutropaenia, severe congenital 3, autosomal recessive, MIM# 610738; Kostmann syndrome MONDO:0012548
Mendeliome v0.8055 HAX1 Zornitza Stark Publications for gene: HAX1 were set to
Mendeliome v0.8054 HAX1 Zornitza Stark Mode of inheritance for gene: HAX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8053 HAX1 Zornitza Stark reviewed gene: HAX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17187068, 18611981, 19036076; Phenotypes: Neutropaenia, severe congenital 3, autosomal recessive, MIM# 610738, Kostmann syndrome MONDO:0012548; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8053 NFS1 Zornitza Stark Phenotypes for gene: NFS1 were changed from Complex II/III deficiency; multisystem organ failure to Combined oxidative phosphorylation deficiency 52, MIM#619386; Complex II/III deficiency; multisystem organ failure
Mendeliome v0.8052 NFS1 Zornitza Stark Publications for gene: NFS1 were set to 24498631
Mendeliome v0.8051 NFS1 Zornitza Stark edited their review of gene: NFS1: Changed phenotypes: Combined oxidative phosphorylation deficiency 52, MIM#619386, Complex II/III deficiency, multisystem organ failure
Mendeliome v0.8051 DNAJC30 Zornitza Stark Phenotypes for gene: DNAJC30 were changed from Leber Hereditary Optic Neuropathy to Leber Hereditary Optic Neuropathy, MIM#619382
Mendeliome v0.8050 DNAJC30 Zornitza Stark edited their review of gene: DNAJC30: Changed phenotypes: Leber Hereditary Optic Neuropathy, MIM#619382
Mendeliome v0.8050 MYL9 Zornitza Stark Phenotypes for gene: MYL9 were changed from Megacystis-microcolon-intestinal hypoperistalsis syndrome to Megacystis-microcolon-intestinal hypoperistalsis syndrome, MIM#619365
Mendeliome v0.8049 MYL9 Zornitza Stark edited their review of gene: MYL9: Changed phenotypes: Megacystis-microcolon-intestinal hypoperistalsis syndrome, MIM#619365
Mendeliome v0.8049 ARCN1 Zornitza Stark Phenotypes for gene: ARCN1 were changed from to Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay (MIM#617164)
Mendeliome v0.8048 ARCN1 Zornitza Stark Publications for gene: ARCN1 were set to
Mendeliome v0.8047 ARCN1 Zornitza Stark Mode of inheritance for gene: ARCN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8046 ARCN1 Zornitza Stark reviewed gene: ARCN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27476655, 33154040; Phenotypes: Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay (MIM#617164); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8046 NBEAL2 Zornitza Stark Marked gene: NBEAL2 as ready
Mendeliome v0.8046 NBEAL2 Zornitza Stark Gene: nbeal2 has been classified as Green List (High Evidence).
Mendeliome v0.8046 NBEAL2 Zornitza Stark Phenotypes for gene: NBEAL2 were changed from to Gray platelet syndrome, MIM# 139090
Mendeliome v0.8045 NBEAL2 Zornitza Stark Publications for gene: NBEAL2 were set to
Mendeliome v0.8044 NBEAL2 Zornitza Stark Mode of inheritance for gene: NBEAL2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8043 NBEAL2 Zornitza Stark reviewed gene: NBEAL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21765412, 21765411, 21765413; Phenotypes: Gray platelet syndrome, MIM# 139090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8043 GFI1 Zornitza Stark Marked gene: GFI1 as ready
Mendeliome v0.8043 GFI1 Zornitza Stark Gene: gfi1 has been classified as Green List (High Evidence).
Mendeliome v0.8043 GFI1 Zornitza Stark Phenotypes for gene: GFI1 were changed from to Neutropaenia, severe congenital 2, autosomal dominant, MIM# 613107
Mendeliome v0.8042 GFI1 Zornitza Stark Publications for gene: GFI1 were set to
Mendeliome v0.8041 GFI1 Zornitza Stark Mode of inheritance for gene: GFI1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8040 GFI1 Zornitza Stark reviewed gene: GFI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12778173, 20560965, 11810106, 22684987; Phenotypes: Neutropaenia, severe congenital 2, autosomal dominant, MIM# 613107; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8040 SLC13A5 Zornitza Stark Marked gene: SLC13A5 as ready
Mendeliome v0.8040 SLC13A5 Zornitza Stark Gene: slc13a5 has been classified as Green List (High Evidence).
Mendeliome v0.8040 SLC13A5 Zornitza Stark Phenotypes for gene: SLC13A5 were changed from to Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta MIM#615905; MONDO:0014392
Mendeliome v0.8039 SLC13A5 Zornitza Stark Publications for gene: SLC13A5 were set to
Mendeliome v0.8038 SLC13A5 Zornitza Stark Mode of inheritance for gene: SLC13A5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8037 SLC13A5 Zornitza Stark reviewed gene: SLC13A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 24995870, 26384929; Phenotypes: Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta MIM#615905, MONDO:0014392; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8037 GATA2 Zornitza Stark Marked gene: GATA2 as ready
Mendeliome v0.8037 GATA2 Zornitza Stark Gene: gata2 has been classified as Green List (High Evidence).
Mendeliome v0.8037 GATA2 Zornitza Stark Phenotypes for gene: GATA2 were changed from to Immunodeficiency 21, MIM# 614172; GATA2 deficiency with susceptibility to MDS/AML MONDO:0042982; Emberger syndrome, MIM# 614038; Deafness-lymphoedema-leukaemia syndrome MONDO:0013540
Mendeliome v0.8036 GATA2 Zornitza Stark Publications for gene: GATA2 were set to
Mendeliome v0.8035 GATA2 Zornitza Stark Mode of inheritance for gene: GATA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8034 GATA2 Zornitza Stark reviewed gene: GATA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21670465, 21242295, 21892158; Phenotypes: Immunodeficiency 21, MIM# 614172, GATA2 deficiency with susceptibility to MDS/AML MONDO:0042982, Emberger syndrome, MIM# 614038, Deafness-lymphoedema-leukaemia syndrome MONDO:0013540; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8034 GATA1 Zornitza Stark Marked gene: GATA1 as ready
Mendeliome v0.8034 GATA1 Zornitza Stark Gene: gata1 has been classified as Green List (High Evidence).
Mendeliome v0.8034 GATA1 Zornitza Stark Phenotypes for gene: GATA1 were changed from to Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367
Mendeliome v0.8033 GATA1 Zornitza Stark Mode of inheritance for gene: GATA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8032 GATA1 Zornitza Stark reviewed gene: GATA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8032 ELANE Zornitza Stark Marked gene: ELANE as ready
Mendeliome v0.8032 ELANE Zornitza Stark Gene: elane has been classified as Green List (High Evidence).
Mendeliome v0.8032 ELANE Zornitza Stark Phenotypes for gene: ELANE were changed from to Neutropaenia, severe congenital 1, autosomal dominant, MIM# 202700
Mendeliome v0.8031 ELANE Zornitza Stark Publications for gene: ELANE were set to
Mendeliome v0.8030 ELANE Zornitza Stark Mode of inheritance for gene: ELANE was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8029 ELANE Zornitza Stark reviewed gene: ELANE: Rating: GREEN; Mode of pathogenicity: None; Publications: 19036076; Phenotypes: Neutropaenia, severe congenital 1, autosomal dominant, MIM# 202700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8029 EFL1 Zornitza Stark Marked gene: EFL1 as ready
Mendeliome v0.8029 EFL1 Zornitza Stark Gene: efl1 has been classified as Green List (High Evidence).
Mendeliome v0.8029 EFL1 Zornitza Stark Phenotypes for gene: EFL1 were changed from to Shwachman-Diamond syndrome 2, MIM# 617941
Mendeliome v0.8028 EFL1 Zornitza Stark Publications for gene: EFL1 were set to
Mendeliome v0.8027 EFL1 Zornitza Stark Mode of inheritance for gene: EFL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8026 EFL1 Zornitza Stark reviewed gene: EFL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28331068, 31151987; Phenotypes: Shwachman-Diamond syndrome 2, MIM# 617941; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8026 CXCR4 Zornitza Stark Marked gene: CXCR4 as ready
Mendeliome v0.8026 CXCR4 Zornitza Stark Gene: cxcr4 has been classified as Green List (High Evidence).
Mendeliome v0.8026 CXCR4 Zornitza Stark Phenotypes for gene: CXCR4 were changed from to WHIM syndrome, MIM# 193670
Mendeliome v0.8025 CXCR4 Zornitza Stark Publications for gene: CXCR4 were set to
Mendeliome v0.8024 CXCR4 Zornitza Stark Mode of inheritance for gene: CXCR4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8023 CXCR4 Zornitza Stark reviewed gene: CXCR4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12692554; Phenotypes: WHIM syndrome, MIM# 193670; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8023 CTC1 Zornitza Stark Marked gene: CTC1 as ready
Mendeliome v0.8023 CTC1 Zornitza Stark Gene: ctc1 has been classified as Green List (High Evidence).
Mendeliome v0.8023 CTC1 Zornitza Stark Phenotypes for gene: CTC1 were changed from to Cerebroretinal microangiopathy with calcifications and cysts, MIM# 612199
Mendeliome v0.8022 CTC1 Zornitza Stark Publications for gene: CTC1 were set to
Mendeliome v0.8021 CTC1 Zornitza Stark Mode of inheritance for gene: CTC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8020 CTC1 Zornitza Stark reviewed gene: CTC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22267198, 22387016; Phenotypes: Cerebroretinal microangiopathy with calcifications and cysts, MIM# 612199; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8020 ANKRD26 Zornitza Stark Marked gene: ANKRD26 as ready
Mendeliome v0.8020 ANKRD26 Zornitza Stark Gene: ankrd26 has been classified as Green List (High Evidence).
Mendeliome v0.8020 ANKRD26 Zornitza Stark Phenotypes for gene: ANKRD26 were changed from to Thrombocytopaenia 2, MIM# 188000
Mendeliome v0.8019 ANKRD26 Zornitza Stark Publications for gene: ANKRD26 were set to
Mendeliome v0.8018 ANKRD26 Zornitza Stark Mode of inheritance for gene: ANKRD26 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8017 ANKRD26 Zornitza Stark Tag 5'UTR tag was added to gene: ANKRD26.
Mendeliome v0.8017 ANKRD26 Zornitza Stark reviewed gene: ANKRD26: Rating: GREEN; Mode of pathogenicity: None; Publications: 21211618; Phenotypes: Thrombocytopaenia 2, MIM# 188000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8017 AK2 Zornitza Stark Marked gene: AK2 as ready
Mendeliome v0.8017 AK2 Zornitza Stark Gene: ak2 has been classified as Green List (High Evidence).
Mendeliome v0.8017 AK2 Zornitza Stark Phenotypes for gene: AK2 were changed from to Reticular dysgenesis, MIM# 267500
Mendeliome v0.8016 AK2 Zornitza Stark Publications for gene: AK2 were set to
Mendeliome v0.8015 AK2 Zornitza Stark Mode of inheritance for gene: AK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8014 AK2 Zornitza Stark reviewed gene: AK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19043416; Phenotypes: Reticular dysgenesis, MIM# 267500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8014 ADA2 Zornitza Stark Marked gene: ADA2 as ready
Mendeliome v0.8014 ADA2 Zornitza Stark Gene: ada2 has been classified as Green List (High Evidence).
Mendeliome v0.8014 ADA2 Zornitza Stark Phenotypes for gene: ADA2 were changed from to Vasculitis, autoinflammation, immunodeficiency, and haematologic defects syndrome, MIM# 615688
Mendeliome v0.8013 ADA2 Zornitza Stark Publications for gene: ADA2 were set to
Mendeliome v0.8012 ADA2 Zornitza Stark Mode of inheritance for gene: ADA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8011 ADA2 Zornitza Stark commented on gene: ADA2: Vasculitis, autoinflammation, immunodeficiency, and haematologic defects syndrome (VAIHS) is an autosomal recessive multisystem disorder with onset in childhood. The phenotype is highly variable, but most patients have features of a systemic vascular inflammatory disorder with skin ulceration and recurrent strokes affecting the small vessels of the brain resulting in neurologic dysfunction. Other features may include recurrent fever, elevated acute-phase proteins, myalgias, lesions resembling polyarteritis nodosa, and/or livedo racemosa or reticularis with an inflammatory vasculitis on biopsy. Some patients may have renal and/or gastrointestinal involvement, hypertension, aneurysms, or ischemic necrosis of the digits. Some affected individuals have immunodeficiency. At least 10 unrelated families reported, the p.Gly47Arg variant is a common founder variant in the Jewish population.
Mendeliome v0.8011 ADA2 Zornitza Stark reviewed gene: ADA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24552284, 24552285, 33791889; Phenotypes: Vasculitis, autoinflammation, immunodeficiency, and haematologic defects syndrome, MIM# 615688; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8011 IFT74 Zornitza Stark Phenotypes for gene: IFT74 were changed from Bardet-Biedl syndrome 20, MIM# 617119 to Bardet-Biedl syndrome 20, MIM# 617119; Joubert syndrome
Mendeliome v0.8010 IFT74 Zornitza Stark Publications for gene: IFT74 were set to 27486776; 32144365
Mendeliome v0.8009 IFT74 Zornitza Stark edited their review of gene: IFT74: Added comment: PMID 33531668: Identified IFT74 as a JBTS-associated gene in 3 unrelated families through WES. All the affected individuals carried truncated variants and shared one missense variant (p.Q179E) found only in East Asians. The expression of the human p.Q179E-IFT74 variant displayed compromised rescue effects in zebrafish ift74 morphants. Attenuated ciliogenesis; altered distribution of IFT proteins and ciliary membrane proteins, including ARL13B, INPP5E, and GPR161; and disrupted hedgehog signaling were observed in patient fibroblasts with IFT74 variants.; Changed publications: 27486776, 32144365, 33531668; Changed phenotypes: Bardet-Biedl syndrome 20, MIM# 617119, Joubert syndrome
Mendeliome v0.8009 RFX4 Zornitza Stark Marked gene: RFX4 as ready
Mendeliome v0.8009 RFX4 Zornitza Stark Gene: rfx4 has been classified as Green List (High Evidence).
Mendeliome v0.8009 RFX4 Zornitza Stark Classified gene: RFX4 as Green List (high evidence)
Mendeliome v0.8009 RFX4 Zornitza Stark Gene: rfx4 has been classified as Green List (High Evidence).
Mendeliome v0.8008 RFX4 Zornitza Stark gene: RFX4 was added
gene: RFX4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RFX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RFX4 were set to 33658631
Phenotypes for gene: RFX4 were set to ID, ASD, ADHD
Review for gene: RFX4 was set to GREEN
Added comment: Report of 38 individuals (from 33 unrelated families) with de novo or inherited loss of function variants in RFX3 (15 families), RFX4 (4 families), and RFX7 (14 families), identified through WES. Individuals share neurobehavioural features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. These genes are potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.
Sources: Literature
Mendeliome v0.8007 RFX3 Zornitza Stark Marked gene: RFX3 as ready
Mendeliome v0.8007 RFX3 Zornitza Stark Gene: rfx3 has been classified as Green List (High Evidence).
Mendeliome v0.8007 RFX3 Zornitza Stark Classified gene: RFX3 as Green List (high evidence)
Mendeliome v0.8007 RFX3 Zornitza Stark Gene: rfx3 has been classified as Green List (High Evidence).
Mendeliome v0.8006 RFX3 Zornitza Stark gene: RFX3 was added
gene: RFX3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RFX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RFX3 were set to 33658631
Phenotypes for gene: RFX3 were set to ID, ASD, ADHD
Review for gene: RFX3 was set to GREEN
Added comment: Report of 38 individuals (from 33 unrelated families) with de novo or inherited loss of function variants in RFX3 (15 families), RFX4 (4 families), and RFX7 (14 families), identified through WES. Individuals share neurobehavioural features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. These genes are potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.
Sources: Literature
Mendeliome v0.8005 RFX7 Zornitza Stark Marked gene: RFX7 as ready
Mendeliome v0.8005 RFX7 Zornitza Stark Gene: rfx7 has been classified as Green List (High Evidence).
Mendeliome v0.8005 RFX7 Zornitza Stark Classified gene: RFX7 as Green List (high evidence)
Mendeliome v0.8005 RFX7 Zornitza Stark Gene: rfx7 has been classified as Green List (High Evidence).
Mendeliome v0.8004 RFX7 Zornitza Stark gene: RFX7 was added
gene: RFX7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RFX7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RFX7 were set to 33658631
Phenotypes for gene: RFX7 were set to ID, ASD, ADHD
Review for gene: RFX7 was set to GREEN
Added comment: Report of 38 individuals (from 33 unrelated families) with de novo or inherited loss of function variants in RFX3 (15 families), RFX4 (4 families), and RFX7 (14 families), identified through WES. Individuals share neurobehavioural features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. These genes are potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.
Sources: Literature
Mendeliome v0.8003 SEMA3F Zornitza Stark Marked gene: SEMA3F as ready
Mendeliome v0.8003 SEMA3F Zornitza Stark Gene: sema3f has been classified as Green List (High Evidence).
Mendeliome v0.8003 SEMA3F Zornitza Stark Classified gene: SEMA3F as Green List (high evidence)
Mendeliome v0.8003 SEMA3F Zornitza Stark Gene: sema3f has been classified as Green List (High Evidence).
Mendeliome v0.8002 SEMA3F Zornitza Stark gene: SEMA3F was added
gene: SEMA3F was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEMA3F was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEMA3F were set to 33495532
Phenotypes for gene: SEMA3F were set to Hypogonadotropic hypogonadism
Review for gene: SEMA3F was set to GREEN
Added comment: Screened 216 patients with Idiopathic hypogonadotropic hypogonadism by exome sequencing. Identified 10 individuals from 7 families with heterozygous SEMA3F missense variants. In 4 of the kindreds, there was at least one more gene known to be associated with IHH (oligogenecity). Provide unequivocal human embryonic data showing the expression of SEMA3F along the developing human GnRH migratory pathway. SEMA3Fs harboring the P452T, T29M, and T724M missense variants showed impaired SEMA3F secretion in whole cell lysates.
Sources: Literature
Mendeliome v0.8001 PLXNA3 Zornitza Stark Marked gene: PLXNA3 as ready
Mendeliome v0.8001 PLXNA3 Zornitza Stark Gene: plxna3 has been classified as Green List (High Evidence).
Mendeliome v0.8001 PLXNA3 Zornitza Stark Classified gene: PLXNA3 as Green List (high evidence)
Mendeliome v0.8001 PLXNA3 Zornitza Stark Gene: plxna3 has been classified as Green List (High Evidence).
Mendeliome v0.8000 PLXNA3 Zornitza Stark gene: PLXNA3 was added
gene: PLXNA3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLXNA3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PLXNA3 were set to 33495532
Phenotypes for gene: PLXNA3 were set to Hypogonadotropic hypogonadism
Review for gene: PLXNA3 was set to GREEN
Added comment: Screened 216 patients with Idiopathic hypogonadotropic hypogonadism by exome sequencing. Identified 7 individuals from 5 families with hemizygous PLXNA3 missense variants. In 2 of the kindreds, there was at least one more gene known to be associated with IHH (oligogenecity). Data provided with evidence that PLXNA3, a key component of the SEMA3F holoreceptor complex,31 is expressed by the human GnRH and olfactory/vomeronasal systems. S646P variant showed PLXNA3 localization exclusively in the ER, indicating that the variant S646P disrupts cell surface localization of PLXNA3.
Sources: Literature
Mendeliome v0.7999 DLG4 Zornitza Stark Phenotypes for gene: DLG4 were changed from Intellectual disability; Marfanoid habitus to Intellectual developmental disorder 62, MIM# 618793
Mendeliome v0.7998 DLG4 Zornitza Stark Publications for gene: DLG4 were set to 27479843; 25123844; 19617690; 29460436; 23020937; 28135719
Mendeliome v0.7997 DLG4 Zornitza Stark edited their review of gene: DLG4: Added comment: PMID 33597769: 53 patients (42 previously unpublished) with DLG4 variants. The clinical picture predominated by early onset global developmental delay, intellectual disability, autism spectrum disorder, and attention deficit–hyperactivity disorder.; Changed publications: 27479843, 25123844, 19617690, 29460436, 23020937, 28135719, 33597769; Changed phenotypes: Intellectual developmental disorder 62, MIM# 618793
Mendeliome v0.7997 GNAI1 Zornitza Stark Marked gene: GNAI1 as ready
Mendeliome v0.7997 GNAI1 Zornitza Stark Gene: gnai1 has been classified as Green List (High Evidence).
Mendeliome v0.7997 GNAI1 Zornitza Stark Phenotypes for gene: GNAI1 were changed from to Intellectual disability; seizures; hypotonia
Mendeliome v0.7996 GNAI1 Zornitza Stark Publications for gene: GNAI1 were set to
Mendeliome v0.7995 GNAI1 Zornitza Stark Mode of inheritance for gene: GNAI1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7994 GNAI1 Zornitza Stark reviewed gene: GNAI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28135719, 33473207; Phenotypes: Intellectual disability, seizures, hypotonia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7994 SURF1 Elena Savva reviewed gene: SURF1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24027061; Phenotypes: Charcot-Marie-Tooth disease, type 4K MIM#616684, Mitochondrial complex IV deficiency, nuclear type 1 MIM#220110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.7994 FARSA Zornitza Stark Classified gene: FARSA as Green List (high evidence)
Mendeliome v0.7994 FARSA Zornitza Stark Gene: farsa has been classified as Green List (High Evidence).
Mendeliome v0.7993 FARSA Zornitza Stark edited their review of gene: FARSA: Added comment: Schuch et al. (2021) report 3 unrelated individuals with bi-allelic variants in FARSA. Identified through WES and variants segregated with disease. Functional evidence was obtained with reduced FARS1 enzyme activity levels in fibroblasts or EBV-transformed lymphoblastoid cell lines (EBV-LCLs) of patients. Common to all was a chronic interstitial lung disease starting early in life and characterized by bilateral ground-glass opacification on HR-CT, and cholesterol pneumonitis in lung histology. Additional abnormalities in other organ systems include liver disease, neurological manifestations, and growth restriction.; Changed rating: GREEN; Changed publications: 31355908, 33598926; Changed phenotypes: Rajab interstitial lung disease with brain calcifications 2, MIM# 619013
Mendeliome v0.7993 LAMA5 Bryony Thompson Phenotypes for gene: LAMA5 were changed from to bent bone dysplasia; nephrotic syndrome; Presynaptic congenital myasthenic syndrome; multisystem syndrome; developmental delay
Mendeliome v0.7992 LAMA5 Bryony Thompson Publications for gene: LAMA5 were set to
Mendeliome v0.7991 LAMA5 Bryony Thompson Mode of inheritance for gene: LAMA5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7990 LAMA5 Bryony Thompson reviewed gene: LAMA5: Rating: AMBER; Mode of pathogenicity: None; Publications: 33242826, 29534211, 16790509, 30589377, 28735299, 30631761; Phenotypes: bent bone dysplasia, nephrotic syndrome, Presynaptic congenital myasthenic syndrome, multisystem syndrome, developmental delay; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7990 ZNF81 Zornitza Stark Marked gene: ZNF81 as ready
Mendeliome v0.7990 ZNF81 Zornitza Stark Gene: znf81 has been classified as Red List (Low Evidence).
Mendeliome v0.7990 ZNF81 Zornitza Stark Phenotypes for gene: ZNF81 were changed from to Intellectual disability
Mendeliome v0.7989 ZNF81 Zornitza Stark Publications for gene: ZNF81 were set to
Mendeliome v0.7988 ZNF81 Zornitza Stark Mode of inheritance for gene: ZNF81 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7987 ZNF81 Zornitza Stark Classified gene: ZNF81 as Red List (low evidence)
Mendeliome v0.7987 ZNF81 Zornitza Stark Gene: znf81 has been classified as Red List (Low Evidence).
Mendeliome v0.7986 ZNF81 Zornitza Stark reviewed gene: ZNF81: Rating: RED; Mode of pathogenicity: None; Publications: 15121780; Phenotypes: Intellectual disability; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7986 RELN Ee Ming Wong edited their review of gene: RELN: Added comment: - Six affected individuals carrying missense variants in RELN including
1. Two individuals with compound heterozygous variants
- One of the variants has 26 homozygotes in gnomAD and therefore pathogenicity of this variant is in question
- LoF demonstrated for three of the variants (reduced RELN secretion), except for p.Y1821H which demonstrated an apparently increased RELN secretion (GoF)
2. Two brothers carrying the maternally inherited variant (mother apparently healthy)
- LoF demonstrated for these variants
3. Two individuals de novo for RELN variants
- Dominant negative demonstrated for these variants where secretion of WT-RELN was impaired when co-transfected with mutant constructs in HEK293T cells; Changed rating: AMBER; Changed publications: Riva et al bioRxiv (pre-print, not peer-reviewed); Changed phenotypes: Pachygyria, Polymicrogyria, Heterotopia; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7986 NIID Bryony Thompson Marked STR: NIID as ready
Mendeliome v0.7986 NIID Bryony Thompson Str: niid has been classified as Green List (High Evidence).
Mendeliome v0.7986 NIID Bryony Thompson Classified STR: NIID as Green List (high evidence)
Mendeliome v0.7986 NIID Bryony Thompson Str: niid has been classified as Green List (High Evidence).
Mendeliome v0.7985 NIID Bryony Thompson STR: NIID was added
STR: NIID was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: NIID was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: NIID were set to 31178126; 31332381; 31819945; 33887199; 33943039; 32250060; 31332380; 32852534; 32989102
Phenotypes for STR: NIID were set to Neuronal intranuclear inclusion disease MIM#603472; Tremor, hereditary essential, 6 MIM#618866
Review for STR: NIID was set to GREEN
STR: NIID was marked as clinically relevant
Added comment: NM_001364012.2:c.-164GGC[(66_517)]
Large number of families and sporadic cases reported with expansions, with a range of neurodegenerative phenotypes, including: dementia, Parkinsonism/tremor, peripheral neuropathy, leukoencephalopathy, myopathy, motor neurone disease.
Normal repeat range: 7-60
Pathogenic repeat range: >=61-500
Mechanism of disease is translation of repeat expansion into a toxic polyglycine protein, identified in both mouse models and tissue samples from affected individuals.
Sources: Literature
Mendeliome v0.7984 NOTCH2NL Bryony Thompson Classified gene: NOTCH2NL as No list
Mendeliome v0.7984 NOTCH2NL Bryony Thompson Added comment: Comment on list classification: STR is the only reported cause of disease for this gene. It has been added as an STR under NIID.
Mendeliome v0.7984 NOTCH2NL Bryony Thompson Gene: notch2nl has been removed from the panel.
Mendeliome v0.7983 TRPM6 Zornitza Stark Marked gene: TRPM6 as ready
Mendeliome v0.7983 TRPM6 Zornitza Stark Gene: trpm6 has been classified as Green List (High Evidence).
Mendeliome v0.7983 TRPM6 Zornitza Stark Phenotypes for gene: TRPM6 were changed from to Hypomagnesaemia 1, intestinal (MIM#602014)
Mendeliome v0.7982 TRPM6 Zornitza Stark Mode of inheritance for gene: TRPM6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7981 CNTNAP1 Zornitza Stark Marked gene: CNTNAP1 as ready
Mendeliome v0.7981 CNTNAP1 Zornitza Stark Gene: cntnap1 has been classified as Green List (High Evidence).
Mendeliome v0.7981 CNTNAP1 Zornitza Stark Phenotypes for gene: CNTNAP1 were changed from to Hypomyelinating neuropathy, congenital, 3, MIM#618186; Lethal congenital contracture syndrome 7, MIM# 616286
Mendeliome v0.7980 CNTNAP1 Zornitza Stark Publications for gene: CNTNAP1 were set to
Mendeliome v0.7979 CNTNAP1 Zornitza Stark Mode of inheritance for gene: CNTNAP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7978 CNTNAP1 Zornitza Stark reviewed gene: CNTNAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28374019, 29511323, 27668699; Phenotypes: Hypomyelinating neuropathy, congenital, 3, MIM#618186, Lethal congenital contracture syndrome 7, MIM# 616286; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7978 GLDN Zornitza Stark Marked gene: GLDN as ready
Mendeliome v0.7978 GLDN Zornitza Stark Gene: gldn has been classified as Green List (High Evidence).
Mendeliome v0.7978 GLDN Zornitza Stark Phenotypes for gene: GLDN were changed from to Lethal congenital contracture syndrome 11, MIM# 617194; MONDO:0014965
Mendeliome v0.7977 GLDN Zornitza Stark Publications for gene: GLDN were set to
Mendeliome v0.7976 GLDN Zornitza Stark Mode of inheritance for gene: GLDN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7975 GLDN Zornitza Stark reviewed gene: GLDN: Rating: GREEN; Mode of pathogenicity: None; Publications: 27616481, 32812332, 28726266; Phenotypes: Lethal congenital contracture syndrome 11, MIM# 617194, MONDO:0014965; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7975 ZBTB42 Zornitza Stark Marked gene: ZBTB42 as ready
Mendeliome v0.7975 ZBTB42 Zornitza Stark Gene: zbtb42 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7975 ZBTB42 Zornitza Stark Classified gene: ZBTB42 as Amber List (moderate evidence)
Mendeliome v0.7975 ZBTB42 Zornitza Stark Gene: zbtb42 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7974 ZBTB42 Zornitza Stark gene: ZBTB42 was added
gene: ZBTB42 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ZBTB42 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZBTB42 were set to 25055871
Phenotypes for gene: ZBTB42 were set to Lethal congenital contracture syndrome 6, MIM# 616248
Review for gene: ZBTB42 was set to AMBER
Added comment: Homozygous missense variant reported in a family with three stillbirths and a phenotype consistent with LCCS. Supportive zebrafish model.
Sources: Expert Review
Mendeliome v0.7973 MYBPC1 Zornitza Stark Marked gene: MYBPC1 as ready
Mendeliome v0.7973 MYBPC1 Zornitza Stark Gene: mybpc1 has been classified as Green List (High Evidence).
Mendeliome v0.7973 MYBPC1 Zornitza Stark Phenotypes for gene: MYBPC1 were changed from to Arthrogryposis, distal, type 1B 614335; Lethal congenital contracture syndrome 4, MIM# 614915; Myopathy, congenital, with tremor MIM#618524
Mendeliome v0.7972 MYBPC1 Zornitza Stark Publications for gene: MYBPC1 were set to
Mendeliome v0.7971 MYBPC1 Zornitza Stark Mode of inheritance for gene: MYBPC1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7970 MYBPC1 Zornitza Stark reviewed gene: MYBPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20045868, 22610851, 23873045, 26661508, 31264822, 31025394; Phenotypes: Arthrogryposis, distal, type 1B 614335, Lethal congenital contracture syndrome 4, MIM# 614915, Myopathy, congenital, with tremor MIM#618524; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7970 ERBB3 Zornitza Stark Marked gene: ERBB3 as ready
Mendeliome v0.7970 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Green List (High Evidence).
Mendeliome v0.7970 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from Lethal congenital contractural syndrome 2, MIM# 607598 to Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis
Mendeliome v0.7969 ERBB3 Zornitza Stark Publications for gene: ERBB3 were set to 17701904; 31752936
Mendeliome v0.7968 ADCY6 Zornitza Stark Phenotypes for gene: ADCY6 were changed from Lethal congenital contracture syndrome 8, OMIM # 616287 to Lethal congenital contracture syndrome 8, OMIM # 616287; MONDO:0014570
Mendeliome v0.7967 ADGRG6 Zornitza Stark edited their review of gene: ADGRG6: Changed phenotypes: Lethal congenital contracture syndrome 9, MIM #616503, MONDO:0014670
Mendeliome v0.7967 TRPM6 Kristin Rigbye reviewed gene: TRPM6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypomagnesemia 1, intestinal (MIM#602014), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7967 MUSK Zornitza Stark Marked gene: MUSK as ready
Mendeliome v0.7967 MUSK Zornitza Stark Gene: musk has been classified as Green List (High Evidence).
Mendeliome v0.7967 MUSK Zornitza Stark Phenotypes for gene: MUSK were changed from to Fetal akinesia deformation sequence 1, MIM# 208150; MONDO:0100101; Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency, MIM# 616325; MONDO:0014587
Mendeliome v0.7966 MUSK Zornitza Stark Publications for gene: MUSK were set to
Mendeliome v0.7965 MUSK Zornitza Stark Mode of inheritance for gene: MUSK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7964 MUSK Zornitza Stark reviewed gene: MUSK: Rating: GREEN; Mode of pathogenicity: None; Publications: 25537362, 25612909, 8653786, 31750350, 15496425, 19949040, 20371544, 32253145; Phenotypes: Fetal akinesia deformation sequence 1, MIM# 208150, MONDO:0100101, Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency, MIM# 616325, MONDO:0014587; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7964 DOK7 Zornitza Stark Marked gene: DOK7 as ready
Mendeliome v0.7964 DOK7 Zornitza Stark Gene: dok7 has been classified as Green List (High Evidence).
Mendeliome v0.7964 DOK7 Zornitza Stark Phenotypes for gene: DOK7 were changed from to Myasthenic syndrome, congenital, 10, MIM# 254300; Fetal akinesia deformation sequence 3, MIM# 618389
Mendeliome v0.7963 DOK7 Zornitza Stark Publications for gene: DOK7 were set to
Mendeliome v0.7962 DOK7 Zornitza Stark Mode of inheritance for gene: DOK7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7961 DOK7 Zornitza Stark reviewed gene: DOK7: Rating: GREEN; Mode of pathogenicity: None; Publications: 16917026, 18626973, 20147321, 16794080, 31453852, 29395672, 32360404, 19261599, 31880392; Phenotypes: Myasthenic syndrome, congenital, 10, MIM# 254300, Fetal akinesia deformation sequence 3, MIM# 618389; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7961 TPM2 Zornitza Stark Marked gene: TPM2 as ready
Mendeliome v0.7961 TPM2 Zornitza Stark Gene: tpm2 has been classified as Green List (High Evidence).
Mendeliome v0.7961 TPM2 Zornitza Stark Phenotypes for gene: TPM2 were changed from to Arthrogryposis, distal, type 1A 108120; Arthrogryposis, distal, type 2B4 108120; CAP myopathy 2 609285; Nemaline myopathy 4, autosomal dominant 609285; Multiple pterygium syndrome
Mendeliome v0.7960 TPM2 Zornitza Stark Publications for gene: TPM2 were set to
Mendeliome v0.7959 TPM2 Zornitza Stark Mode of inheritance for gene: TPM2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7958 TPM2 Zornitza Stark reviewed gene: TPM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32092148, 27726070, 32092148, 24692096; Phenotypes: Arthrogryposis, distal, type 1A 108120, Arthrogryposis, distal, type 2B4 108120, CAP myopathy 2 609285, Nemaline myopathy 4, autosomal dominant 609285, Multiple pterygium syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7958 CHRNG Zornitza Stark Marked gene: CHRNG as ready
Mendeliome v0.7958 CHRNG Zornitza Stark Gene: chrng has been classified as Green List (High Evidence).
Mendeliome v0.7958 CHRNG Zornitza Stark Phenotypes for gene: CHRNG were changed from to Escobar syndrome, MIM# 265000; Multiple pterygium syndrome, lethal type, MIM# 253290; MONDO:0009926; MONDO:0009668
Mendeliome v0.7957 CHRNG Zornitza Stark Publications for gene: CHRNG were set to
Mendeliome v0.7956 CHRNG Zornitza Stark Mode of inheritance for gene: CHRNG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7955 CHRNG Zornitza Stark reviewed gene: CHRNG: Rating: GREEN; Mode of pathogenicity: None; Publications: 16826520, 16826531, 22167768; Phenotypes: Escobar syndrome, MIM# 265000, Multiple pterygium syndrome, lethal type, MIM# 253290, MONDO:0009926, MONDO:0009668; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7955 CD207 Zornitza Stark Marked gene: CD207 as ready
Mendeliome v0.7955 CD207 Zornitza Stark Gene: cd207 has been classified as Red List (Low Evidence).
Mendeliome v0.7955 CD207 Zornitza Stark Phenotypes for gene: CD207 were changed from to Birbeck granule deficiency, MIM# 613393
Mendeliome v0.7954 CD207 Zornitza Stark Publications for gene: CD207 were set to
Mendeliome v0.7953 CD207 Zornitza Stark Mode of inheritance for gene: CD207 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7952 CD207 Zornitza Stark Classified gene: CD207 as Red List (low evidence)
Mendeliome v0.7952 CD207 Zornitza Stark Gene: cd207 has been classified as Red List (Low Evidence).
Mendeliome v0.7951 CD207 Zornitza Stark reviewed gene: CD207: Rating: RED; Mode of pathogenicity: None; Publications: 15816828; Phenotypes: Birbeck granule deficiency, MIM# 613393; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7951 KIF17 Zornitza Stark Marked gene: KIF17 as ready
Mendeliome v0.7951 KIF17 Zornitza Stark Gene: kif17 has been classified as Red List (Low Evidence).
Mendeliome v0.7951 KIF17 Zornitza Stark gene: KIF17 was added
gene: KIF17 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF17 were set to 33922911; 30458707; 28341548
Phenotypes for gene: KIF17 were set to Microphthalmia; Coloboma
Review for gene: KIF17 was set to RED
Added comment: Two siblings reported with MAC spectrum and homozygous missense variant in this gene. Some pre-existing data linking KIF17 to eye development.
Sources: Literature
Mendeliome v0.7950 SASH3 Zornitza Stark Marked gene: SASH3 as ready
Mendeliome v0.7950 SASH3 Zornitza Stark Gene: sash3 has been classified as Green List (High Evidence).
Mendeliome v0.7950 SASH3 Zornitza Stark Classified gene: SASH3 as Green List (high evidence)
Mendeliome v0.7950 SASH3 Zornitza Stark Gene: sash3 has been classified as Green List (High Evidence).
Mendeliome v0.7949 SASH3 Zornitza Stark gene: SASH3 was added
gene: SASH3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SASH3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SASH3 were set to 33876203
Phenotypes for gene: SASH3 were set to Combined immunodeficiency; immune dysregulation
Review for gene: SASH3 was set to GREEN
Added comment: Four unrelated males reported presenting with combined immunodeficiency and immune dysregulation manifesting as recurrent sinopulmonary, cutaneous and mucosal infections, and refractory autoimmune cytopaenias. One missense variant, rest were nonsense.
Sources: Literature
Mendeliome v0.7948 FOXP1 Zornitza Stark Publications for gene: FOXP1 were set to
Mendeliome v0.7947 FOXP1 Zornitza Stark Mode of inheritance for gene: FOXP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7946 FOXP1 Zornitza Stark changed review comment from: At least 5 unrelated individuals reported.; to: At least 30 unrelated individuals reported.
Mendeliome v0.7946 FOXP1 Zornitza Stark edited their review of gene: FOXP1: Changed publications: 26633542, 28741757, 34109629
Mendeliome v0.7946 FOXP1 Zornitza Stark reviewed gene: FOXP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26633542, 28741757; Phenotypes: Mental retardation with language impairment and with or without autistic features 613670; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7946 PARP6 Zornitza Stark Publications for gene: PARP6 were set to Cells 2021, 10(6), 1289; https://doi.org/10.3390/cells10061289
Mendeliome v0.7945 PARP6 Zornitza Stark edited their review of gene: PARP6: Changed publications: 34067418
Mendeliome v0.7945 DNAH2 Zornitza Stark edited their review of gene: DNAH2: Added comment: PMID 32732226: compound het variants identified in a fetus with hydrops and complex congenital heart disease detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hydrops, heterotaxy, complex congenital heart disease, hypotrophic splenium, and common mesentery.; Changed publications: 30811583, 32732226; Changed phenotypes: Spermatogenic failure 45, MIM# 619094, Heterotaxy
Mendeliome v0.7945 MYBPC2 Zornitza Stark Marked gene: MYBPC2 as ready
Mendeliome v0.7945 MYBPC2 Zornitza Stark Gene: mybpc2 has been classified as Red List (Low Evidence).
Mendeliome v0.7945 MYBPC2 Zornitza Stark gene: MYBPC2 was added
gene: MYBPC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYBPC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYBPC2 were set to 32732226
Phenotypes for gene: MYBPC2 were set to Fetal akinesia; Hydrops; Hygroma; Multiple pterygium
Review for gene: MYBPC2 was set to RED
Added comment: Novel candidate gene identified in a fetus with fetal akinesia detected by ultrasound. Autopsy showed multiple congenital abnormalities including hydrops, hygroma, multiple pterygium. A homozygous variant (c.3394G>A/ p.Glu1132Lys) in MYBPC2 was found by exome sequencing with concordant segregation among one affected sib and two unaffected sibs.
Sources: Literature
Mendeliome v0.7944 SCN7A Zornitza Stark Marked gene: SCN7A as ready
Mendeliome v0.7944 SCN7A Zornitza Stark Gene: scn7a has been classified as Red List (Low Evidence).
Mendeliome v0.7944 SCN7A Zornitza Stark gene: SCN7A was added
gene: SCN7A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SCN7A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCN7A were set to 32732226
Phenotypes for gene: SCN7A were set to Holoprosencephaly
Review for gene: SCN7A was set to RED
Added comment: Novel candidate gene identified in a fetus with holoprosencephaly detected by ultrasound. Autopsy showed multiple congenital abnormalities including IUGR, microcephaly, bilateral, ablepharon, corpus callosum agenesis, myelomeningocele, tracheal atresia, absent nipples, unilateral simian crease, and hypoplastic phalanges. Compound heterozygous variants including a truncating variant were found by exome sequencing with concordant segregation.
Sources: Literature
Mendeliome v0.7943 SPTBN5 Zornitza Stark Marked gene: SPTBN5 as ready
Mendeliome v0.7943 SPTBN5 Zornitza Stark Gene: sptbn5 has been classified as Red List (Low Evidence).
Mendeliome v0.7943 SPTBN5 Zornitza Stark gene: SPTBN5 was added
gene: SPTBN5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPTBN5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPTBN5 were set to 32732226; 28007035
Phenotypes for gene: SPTBN5 were set to Sacral agenesis; congenital anomalies
Review for gene: SPTBN5 was set to RED
Added comment: Identified as a candidate gene in a sacral agenesis cohort.

PMID 32732226: compound het variants identified in a fetus with multicystic kidney and oligohydramnios detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma coli, spina bifida, polycystic kidneys, facial dysmorphism, common mesenterin, rachischisis, sacral vertebral agenesis.
Sources: Literature
Mendeliome v0.7942 WDR91 Zornitza Stark Phenotypes for gene: WDR91 were changed from to Hydrocephalus; cerebellar hypoplasia; hygroma
Mendeliome v0.7941 WDR91 Zornitza Stark Publications for gene: WDR91 were set to
Mendeliome v0.7940 WDR91 Zornitza Stark Mode of inheritance for gene: WDR91 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7939 WDR91 Zornitza Stark Classified gene: WDR91 as Amber List (moderate evidence)
Mendeliome v0.7939 WDR91 Zornitza Stark Gene: wdr91 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7938 WDR91 Zornitza Stark commented on gene: WDR91: PMID 32732226: Novel candidate gene identified in a fetus with hygroma and hydrocephaly detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma, macrocephaly, abnormal ears, unilateral simian crease, hydrocephaly, cerebellar hypoplasia, and interventricular communication. A homozygous truncating variant was found by exome sequencing with concordant segregation among 4 affected fetus, 2 healthy sibs and both parents. Mouse models support role in brain development.
Mendeliome v0.7938 WDR91 Zornitza Stark reviewed gene: WDR91: Rating: AMBER; Mode of pathogenicity: None; Publications: 34028500, 28860274, 32732226; Phenotypes: Hydrocephalus, cerebellar hypoplasia, hygroma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7938 PLEKHN1 Zornitza Stark Marked gene: PLEKHN1 as ready
Mendeliome v0.7938 PLEKHN1 Zornitza Stark Gene: plekhn1 has been classified as Red List (Low Evidence).
Mendeliome v0.7938 PLEKHN1 Zornitza Stark gene: PLEKHN1 was added
gene: PLEKHN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLEKHN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLEKHN1 were set to 33884296
Phenotypes for gene: PLEKHN1 were set to Sensory Neuropathy
Review for gene: PLEKHN1 was set to RED
Added comment: Hom missense variant in single patient with severely reduced/absent pain and temperature sensation
Sources: Literature
Mendeliome v0.7937 ZNF3 Zornitza Stark Marked gene: ZNF3 as ready
Mendeliome v0.7937 ZNF3 Zornitza Stark Gene: znf3 has been classified as Red List (Low Evidence).
Mendeliome v0.7937 SMPDL3A Seb Lunke changed review comment from: Hom missense variant in twin sisters with deverely reduced pain and temperature sensation
Sources: Literature; to: Hom missense variant in twin sisters with severely reduced pain and temperature sensation
Sources: Literature
Mendeliome v0.7937 ZNF3 Zornitza Stark gene: ZNF3 was added
gene: ZNF3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF3 were set to 32732226
Phenotypes for gene: ZNF3 were set to Hydrocephalus; cleft palate; microphthalmia
Review for gene: ZNF3 was set to RED
Added comment: Novel candidate gene identified in a fetus with hydrocephaly and facial cleft detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including a median cleft palate, partial maxillar agenesis, bilateral severe microphthalmia, arhinencephaly, partial thalamic fusion. A homozygous truncating variant (c.396A>G/ p.*132Trpext*69) in ZNF3 was found by exome sequencing.
Sources: Literature
Mendeliome v0.7936 SMPDL3A Seb Lunke Marked gene: SMPDL3A as ready
Mendeliome v0.7936 SMPDL3A Seb Lunke Gene: smpdl3a has been classified as Red List (Low Evidence).
Mendeliome v0.7936 WRAP73 Zornitza Stark Marked gene: WRAP73 as ready
Mendeliome v0.7936 WRAP73 Zornitza Stark Gene: wrap73 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7936 WRAP73 Zornitza Stark Classified gene: WRAP73 as Amber List (moderate evidence)
Mendeliome v0.7936 WRAP73 Zornitza Stark Gene: wrap73 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7936 SMPDL3A Seb Lunke gene: SMPDL3A was added
gene: SMPDL3A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SMPDL3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMPDL3A were set to 33884296
Phenotypes for gene: SMPDL3A were set to Sensory Neuropathy
Added comment: Hom missense variant in twin sisters with deverely reduced pain and temperature sensation
Sources: Literature
Mendeliome v0.7935 WRAP73 Zornitza Stark gene: WRAP73 was added
gene: WRAP73 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WRAP73 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WRAP73 were set to 33693649
Phenotypes for gene: WRAP73 were set to Microsperophakia
Review for gene: WRAP73 was set to AMBER
Added comment: Two Indian families with same homozygous missense, (p.Pro383Leu) and supportive functional data (zebrafish model).
Sources: Literature
Mendeliome v0.7934 EIF2AK2 Zornitza Stark Phenotypes for gene: EIF2AK2 were changed from Intellectual disability; white matter abnormalities; ataxia; regression with febrile illness to Intellectual disability; white matter abnormalities; ataxia; regression with febrile illness; Dystonia
Mendeliome v0.7933 EIF2AK2 Zornitza Stark edited their review of gene: EIF2AK2: Changed publications: 33236446, 33866603
Mendeliome v0.7933 EIF2AK2 Zornitza Stark Publications for gene: EIF2AK2 were set to 32197074
Mendeliome v0.7932 EIF2AK2 Zornitza Stark edited their review of gene: EIF2AK2: Added comment: Four unrelated families reported with dystonia, recurrent variant, (p.Gly130Arg); Changed publications: 32197074, 33866603; Changed phenotypes: Intellectual disability, white matter abnormalities, ataxia, regression with febrile illness, Dystonia
Mendeliome v0.7932 SLC37A4 Zornitza Stark Marked gene: SLC37A4 as ready
Mendeliome v0.7932 SLC37A4 Zornitza Stark Gene: slc37a4 has been classified as Green List (High Evidence).
Mendeliome v0.7932 SLC37A4 Zornitza Stark Phenotypes for gene: SLC37A4 were changed from to Glycogen storage disease Ib 232220; Glycogen storage disease Ic 232240; Congenital disorder of glycosylation
Mendeliome v0.7931 SLC37A4 Zornitza Stark Publications for gene: SLC37A4 were set to
Mendeliome v0.7930 SLC37A4 Zornitza Stark Mode of inheritance for gene: SLC37A4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7929 SLC37A4 Zornitza Stark reviewed gene: SLC37A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 33964207, 9675154, 9758626; Phenotypes: Glycogen storage disease Ib 232220, Glycogen storage disease Ic 232240, Congenital disorder of glycosylation; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7929 TUBA1A Zornitza Stark Marked gene: TUBA1A as ready
Mendeliome v0.7929 TUBA1A Zornitza Stark Gene: tuba1a has been classified as Green List (High Evidence).
Mendeliome v0.7929 TUBA1A Zornitza Stark Phenotypes for gene: TUBA1A were changed from to Lissencephaly 3, MIM# 611603; Congenital fibrosis of the extraocular muscles, AD
Mendeliome v0.7928 TUBA1A Zornitza Stark Publications for gene: TUBA1A were set to
Mendeliome v0.7927 TUBA1A Zornitza Stark Mode of inheritance for gene: TUBA1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7926 TUBA1A Zornitza Stark reviewed gene: TUBA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly 3, MIM# 611603; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7926 COL9A3 Zornitza Stark Phenotypes for gene: COL9A3 were changed from Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969; Stickler syndrome; Deafness to Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969; Stickler syndrome AR; Deafness AD; Peripheral vitreoretinal degeneration and retinal detachment, AD
Mendeliome v0.7925 COL9A3 Zornitza Stark Publications for gene: COL9A3 were set to 30450842; 31090205; 24273071; 10090888; 15551337; 33078831; 15917166
Mendeliome v0.7924 BCAS3 Zornitza Stark Phenotypes for gene: BCAS3 were changed from to Syndromic neurodevelopmental disorder
Mendeliome v0.7923 BCAS3 Zornitza Stark Publications for gene: BCAS3 were set to
Mendeliome v0.7922 BCAS3 Zornitza Stark Mode of inheritance for gene: BCAS3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7921 ANGPTL8 Zornitza Stark Marked gene: ANGPTL8 as ready
Mendeliome v0.7921 ANGPTL8 Zornitza Stark Gene: angptl8 has been classified as Red List (Low Evidence).
Mendeliome v0.7921 ANGPTL8 Zornitza Stark Classified gene: ANGPTL8 as Red List (low evidence)
Mendeliome v0.7921 ANGPTL8 Zornitza Stark Gene: angptl8 has been classified as Red List (Low Evidence).
Mendeliome v0.7920 SRCAP Zornitza Stark Marked gene: SRCAP as ready
Mendeliome v0.7920 SRCAP Zornitza Stark Gene: srcap has been classified as Green List (High Evidence).
Mendeliome v0.7920 SRCAP Zornitza Stark Phenotypes for gene: SRCAP were changed from to Floating-Harbor syndrome MIM#136140; Neurodevelopmental disorder, non-Floating Harbor
Mendeliome v0.7919 SRCAP Zornitza Stark Publications for gene: SRCAP were set to
Mendeliome v0.7918 SRCAP Zornitza Stark Mode of inheritance for gene: SRCAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7917 SRCAP Zornitza Stark reviewed gene: SRCAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 33909990; Phenotypes: Floating-Harbor syndrome MIM#136140, Neurodevelopmental disorder, non-Floating Harbor; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7917 ADAMTSL2 Zornitza Stark Marked gene: ADAMTSL2 as ready
Mendeliome v0.7917 ADAMTSL2 Zornitza Stark Gene: adamtsl2 has been classified as Green List (High Evidence).
Mendeliome v0.7917 ADAMTSL2 Zornitza Stark Phenotypes for gene: ADAMTSL2 were changed from to Geleophysic dysplasia 1, MIM# 231050; Dermatosparaxic Ehlers Danlos syndrome
Mendeliome v0.7916 ADAMTSL2 Zornitza Stark Publications for gene: ADAMTSL2 were set to
Mendeliome v0.7915 ADAMTSL2 Zornitza Stark Mode of inheritance for gene: ADAMTSL2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7914 ADAMTSL2 Zornitza Stark reviewed gene: ADAMTSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33369194, 26879370, 21415077; Phenotypes: Geleophysic dysplasia 1, MIM# 231050, Dermatosparaxic Ehlers Danlos syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7914 UNC45A Zornitza Stark Phenotypes for gene: UNC45A were changed from Cholestasis; Diarrhoea; Bone fragility; Impaired hearing to Osteootohepatoenteric syndrome, MIM# 619377; Cholestasis; Diarrhoea; Bone fragility; Impaired hearing
Mendeliome v0.7913 UNC45A Zornitza Stark edited their review of gene: UNC45A: Changed phenotypes: Osteootohepatoenteric syndrome, MIM# 619377, Cholestasis, Diarrhoea, Bone fragility, Impaired hearing
Mendeliome v0.7913 EIF5A Zornitza Stark Phenotypes for gene: EIF5A were changed from Intellectual disability; microcephaly; dysmorphism to Faundes-Banka syndrome, MIM# 619376; Intellectual disability; microcephaly; dysmorphism
Mendeliome v0.7912 EIF5A Zornitza Stark edited their review of gene: EIF5A: Changed phenotypes: Faundes-Banka syndrome, MIM# 619376, Intellectual disability, microcephaly, dysmorphism
Mendeliome v0.7912 HS3ST6 Zornitza Stark Marked gene: HS3ST6 as ready
Mendeliome v0.7912 HS3ST6 Zornitza Stark Gene: hs3st6 has been classified as Red List (Low Evidence).
Mendeliome v0.7912 HS3ST6 Zornitza Stark gene: HS3ST6 was added
gene: HS3ST6 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: HS3ST6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HS3ST6 were set to 33508266
Phenotypes for gene: HS3ST6 were set to Hereditary angioedema-8 (HAE8), MIM#619367
Review for gene: HS3ST6 was set to RED
Added comment: Three affected individuals from a single family reported, missense variant, no functional data.
Sources: Expert list
Mendeliome v0.7911 MYOF Zornitza Stark Marked gene: MYOF as ready
Mendeliome v0.7911 MYOF Zornitza Stark Gene: myof has been classified as Red List (Low Evidence).
Mendeliome v0.7911 MYOF Zornitza Stark gene: MYOF was added
gene: MYOF was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MYOF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYOF were set to 32542751
Phenotypes for gene: MYOF were set to Hereditary angioedema-7 (HAE7), MIM#619366
Review for gene: MYOF was set to RED
Added comment: Three individuals from one family reported, onset of recurrent episodic swelling of the face, lips, and oral mucosa was in the second decade. Variant was also present in another unaffected family member. Some functional data.
Sources: Expert list
Mendeliome v0.7910 KNG1 Zornitza Stark Marked gene: KNG1 as ready
Mendeliome v0.7910 KNG1 Zornitza Stark Gene: kng1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7910 KNG1 Zornitza Stark Phenotypes for gene: KNG1 were changed from to Hereditary angioedema-6 (HAE6), MIM#619363
Mendeliome v0.7909 KNG1 Zornitza Stark Publications for gene: KNG1 were set to
Mendeliome v0.7908 KNG1 Zornitza Stark Mode of inheritance for gene: KNG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7907 KNG1 Zornitza Stark Classified gene: KNG1 as Amber List (moderate evidence)
Mendeliome v0.7907 KNG1 Zornitza Stark Gene: kng1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7906 KNG1 Zornitza Stark reviewed gene: KNG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31087670, 33114181; Phenotypes: Hereditary angioedema-6 (HAE6), MIM#619363; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7906 ANGPT1 Zornitza Stark Marked gene: ANGPT1 as ready
Mendeliome v0.7906 ANGPT1 Zornitza Stark Gene: angpt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7906 ANGPT1 Zornitza Stark Phenotypes for gene: ANGPT1 were changed from Hereditary angioedema to Hereditary angioedema-5 (HAE5), MIM#619361
Mendeliome v0.7905 ANGPT1 Zornitza Stark reviewed gene: ANGPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Hereditary angioedema-5 (HAE5), MIM#619361; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7905 PLG Zornitza Stark changed review comment from: Association between mono-allelic variants and HAE: Over 20 families reported with a recurrent variant, p.Lys330Glu. Single family reported with a different variant. Note bi-allelic variants are associated with a separate disorder.

Bi-allelic variants and plasminogen deficiency: congenital plasminogen deficiency is characterised clinically by chronic mucosal pseudomembranous lesions consisting of subepithelial fibrin deposition and inflammation. The most common clinical manifestation is ligneous ('wood-like') conjunctivitis, a redness and subsequent formation of pseudomembranes mostly on the palpebral surfaces of the eye that progress to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa. The lesions may be triggered by local injury and/or infection and often recur after local excision. Pseudomembranous lesions of other mucous membranes often occur in the mouth, nasopharynx, trachea, and female genital tract. Some affected children also have congenital occlusive hydrocephalus. At least 3 unrelated families reported.; to: Association between mono-allelic variants and HAE: Over 20 families reported with a recurrent variant, p.Lys330Glu. Single family reported with a different variant. Note bi-allelic variants are associated with a separate disorder.

Bi-allelic variants and plasminogen deficiency: congenital plasminogen deficiency is characterised clinically by chronic mucosal pseudomembranous lesions consisting of subepithelial fibrin deposition and inflammation. The most common clinical manifestation is ligneous ('wood-like') conjunctivitis, a redness and subsequent formation of pseudomembranes mostly on the palpebral surfaces of the eye that progress to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa. The lesions may be triggered by local injury and/or infection and often recur after local excision. Pseudomembranous lesions of other mucous membranes often occur in the mouth, nasopharynx, trachea, and female genital tract. Some affected children also have congenital occlusive hydrocephalus. Over 20 unrelated families reported.
Mendeliome v0.7905 PLG Zornitza Stark edited their review of gene: PLG: Changed publications: 28795768, 29548426, 29987869, 9242524, 10233898, 21174000, 21174000
Mendeliome v0.7905 PLG Zornitza Stark Marked gene: PLG as ready
Mendeliome v0.7905 PLG Zornitza Stark Gene: plg has been classified as Green List (High Evidence).
Mendeliome v0.7905 PLG Zornitza Stark Phenotypes for gene: PLG were changed from to Hereditary angioedema-4 (HAE4), MIM#619360; Plasminogen deficiency, type I, MIM# 217090
Mendeliome v0.7904 PLG Zornitza Stark Publications for gene: PLG were set to
Mendeliome v0.7903 PLG Zornitza Stark Mode of inheritance for gene: PLG was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7902 PLG Zornitza Stark reviewed gene: PLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 28795768, 29548426, 29987869, 9242524, 10233898; Phenotypes: Hereditary angioedema-4 (HAE4), MIM#619360, Plasminogen deficiency, type I, MIM# 217090; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7902 POU4F1 Zornitza Stark Phenotypes for gene: POU4F1 were changed from Ataxia; intention tremor; hypotonia to Childhood-onset ataxia, intention tremor, and hypotonia syndrome (ATITHS) , MIM#619352
Mendeliome v0.7901 POU4F1 Zornitza Stark reviewed gene: POU4F1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Childhood-onset ataxia, intention tremor, and hypotonia syndrome (ATITHS) , MIM#619352; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7901 PRKD1 Zornitza Stark Phenotypes for gene: PRKD1 were changed from Congenital heart defects and ectodermal dysplasia, 617364 to Congenital heart defects and ectodermal dysplasia, 617364; Congenital heart disease, autosomal recessive
Mendeliome v0.7900 PRKD1 Zornitza Stark Publications for gene: PRKD1 were set to 27479907; 32817298
Mendeliome v0.7899 PRKD1 Zornitza Stark Mode of inheritance for gene: PRKD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7898 PIGF Zornitza Stark Phenotypes for gene: PIGF were changed from Glycosylphosphatidylinositol\ deficiency, onychodystrophy, osteodystrophy, intellectual disability, and seizures to Onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome, MIM# 619356
Mendeliome v0.7897 PIGF Zornitza Stark reviewed gene: PIGF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome, MIM# 619356; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7897 PRKD1 Zornitza Stark edited their review of gene: PRKD1: Added comment: Additional publications supporting association with bi-allelic disease:

PMID: 33919081: Three sisters with pulmonary stenosis, truncus arteriosis, and atrial septal defect were homozygous for c.265-1G>T. Their asymptomatic father was also homozygous, however he had two affected sisters (not genotyped), raising the possibility that PRKD1 may undergo autosomal recessive inheritance mode with gender limitation. PMID: 25713110: Two sisters with truncus arteriosis were homozygous for R618X.; Changed publications: 27479907, 32817298, 25713110, 33919081; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7897 ATXN2L Seb Lunke Marked gene: ATXN2L as ready
Mendeliome v0.7897 ATXN2L Seb Lunke Gene: atxn2l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7897 ATXN2L Seb Lunke Classified gene: ATXN2L as Amber List (moderate evidence)
Mendeliome v0.7897 ATXN2L Seb Lunke Gene: atxn2l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7896 ATXN2L Seb Lunke gene: ATXN2L was added
gene: ATXN2L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATXN2L was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATXN2L were set to 33283965; 33057194
Phenotypes for gene: ATXN2L were set to macrocephaly; intellectual disability
Review for gene: ATXN2L was set to AMBER
Added comment: Sources: Literature
Mendeliome v0.7895 LTBP1 Seb Lunke Marked gene: LTBP1 as ready
Mendeliome v0.7895 LTBP1 Seb Lunke Gene: ltbp1 has been classified as Green List (High Evidence).
Mendeliome v0.7895 LTBP1 Seb Lunke Classified gene: LTBP1 as Green List (high evidence)
Mendeliome v0.7895 LTBP1 Seb Lunke Gene: ltbp1 has been classified as Green List (High Evidence).
Mendeliome v0.7894 SLC30A5 Seb Lunke Classified gene: SLC30A5 as Amber List (moderate evidence)
Mendeliome v0.7894 SLC30A5 Seb Lunke Gene: slc30a5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7893 SLC30A5 Seb Lunke Marked gene: SLC30A5 as ready
Mendeliome v0.7893 SLC30A5 Seb Lunke Gene: slc30a5 has been removed from the panel.
Mendeliome v0.7893 CADM3 Seb Lunke Marked gene: CADM3 as ready
Mendeliome v0.7893 CADM3 Seb Lunke Added comment: Comment when marking as ready: Three families, but evidence not that great and missing segregation, so stays amber.
Mendeliome v0.7893 CADM3 Seb Lunke Gene: cadm3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7893 CADM3 Seb Lunke Classified gene: CADM3 as Amber List (moderate evidence)
Mendeliome v0.7893 CADM3 Seb Lunke Gene: cadm3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7892 PGM2L1 Sue White Marked gene: PGM2L1 as ready
Mendeliome v0.7892 PGM2L1 Sue White Gene: pgm2l1 has been classified as Green List (High Evidence).
Mendeliome v0.7892 PGM2L1 Sue White Classified gene: PGM2L1 as Green List (high evidence)
Mendeliome v0.7892 PGM2L1 Sue White Gene: pgm2l1 has been classified as Green List (High Evidence).
Mendeliome v0.7891 BCAS3 Sue White Marked gene: BCAS3 as ready
Mendeliome v0.7891 BCAS3 Sue White Gene: bcas3 has been classified as Green List (High Evidence).
Mendeliome v0.7891 RELN Ee Ming Wong reviewed gene: RELN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25648840; Phenotypes: Myoclonus dystonia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.7891 TUBA1A Kristin Rigbye edited their review of gene: TUBA1A: Changed phenotypes: Congenital fibrosis of the extraocular muscles, AD
Mendeliome v0.7891 TUBA1A Kristin Rigbye reviewed gene: TUBA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 30677308; Phenotypes: Congenital fibrosis of the extraocular muscles; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7891 PGM2L1 Chern Lim reviewed gene: PGM2L1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33979636; Phenotypes: Neurodevelopmental disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.7891 PGM2L1 Chern Lim Deleted their review
Mendeliome v0.7891 LTBP1 Chern Lim gene: LTBP1 was added
gene: LTBP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LTBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LTBP1 were set to 33991472
Phenotypes for gene: LTBP1 were set to cutis laxa syndrome
Review for gene: LTBP1 was set to GREEN
gene: LTBP1 was marked as current diagnostic
Added comment: PMID:33991472
- Premature truncating variants in multiple affected individuals from 4 unrelated consanguineous families.
- Affected individuals present with connective tissue features (cutis laxa and inguinal hernia), craniofacial dysmorphology, variable heart defects, and prominent skeletal features (craniosynostosis, short stature, brachydactyly, and syndactyly).
- Functional studies done on patient fibroblasts and zebrafish models.
Sources: Literature
Mendeliome v0.7891 SLC30A5 Melanie Marty gene: SLC30A5 was added
gene: SLC30A5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC30A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A5 were set to 33547425; 12095919
Phenotypes for gene: SLC30A5 were set to Perinatal lethal cardiomyopathy
Review for gene: SLC30A5 was set to AMBER
Added comment: Four affected children from two unrelated families with cardiomyopathy, hydrops fetalis, or cystic hygroma that all deceased perinatally. 2 different homozygous PTCs variants found. Knockout of SLC30A5 in mouse models showed reduced body growth and reduced bone density. About 60% of the mice died due to bradyarrhythmia.
Sources: Literature
Mendeliome v0.7891 SRCAP Paul De Fazio reviewed gene: SRCAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 33909990; Phenotypes: Floating-Harbor syndrome MIM#136140; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.7891 COL9A3 Kristin Rigbye reviewed gene: COL9A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33633367; Phenotypes: Epiphyseal dysplasia, multiple, 3, with or without myopathy, AD, MIM# 600969, Stickler syndrome, AR, Deafness, AD, Peripheral vitreoretinal degeneration and retinal detachment, AD; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7891 BCAS3 Paul De Fazio reviewed gene: BCAS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 34022130; Phenotypes: Syndromic neurodevelopmental disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.7891 CADM3 Teresa Zhao gene: CADM3 was added
gene: CADM3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CADM3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CADM3 were set to PMID: 33889941
Phenotypes for gene: CADM3 were set to Charcot-Marie-Tooth disease
Review for gene: CADM3 was set to AMBER
Added comment: Three families reported with the same missense variant in CADM3 p.Tyr172Cys (one family de novo), with mice work to show reduced expression of the mutant protein in axons and abnormal axonal organization.
Sources: Literature
Mendeliome v0.7891 ANGPTL8 Dean Phelan gene: ANGPTL8 was added
gene: ANGPTL8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ANGPTL8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANGPTL8 were set to PMID: 33909604
Phenotypes for gene: ANGPTL8 were set to Low serum triglycerides; Coronary artery disease
Review for gene: ANGPTL8 was set to RED
Added comment: PMID: 33909604 - Population studies showed PTV are associated with both lipid levels and coronary artery disease.
Sources: Literature
Mendeliome v0.7891 PGM2L1 Chern Lim gene: PGM2L1 was added
gene: PGM2L1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PGM2L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGM2L1 were set to 33979636
Phenotypes for gene: PGM2L1 were set to severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris
Review for gene: PGM2L1 was set to GREEN
gene: PGM2L1 was marked as current diagnostic
Added comment: PMID: 33979636:
- Hom/chet PTVs in 4 unrelated individuals. All four affected individuals had severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris. Early obesity and seizures were present in three individuals.
- Studies on patient fibroblasts and cell lines indicated that PGM2L1 deficiency causes a decrease, but not a disappearance, of the sugar bisphosphates needed for the formation of NDP-sugars and that there is no evidence that this leads to a glycosylation defect.
Sources: Literature
Mendeliome v0.7891 KCNB1 Zornitza Stark Marked gene: KCNB1 as ready
Mendeliome v0.7891 KCNB1 Zornitza Stark Gene: kcnb1 has been classified as Green List (High Evidence).
Mendeliome v0.7891 KCNB1 Zornitza Stark Phenotypes for gene: KCNB1 were changed from to Epileptic encephalopathy, early infantile, 26, MIM# 616056
Mendeliome v0.7890 KCNB1 Zornitza Stark Publications for gene: KCNB1 were set to
Mendeliome v0.7889 KCNB1 Zornitza Stark Mode of inheritance for gene: KCNB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7888 KCNB1 Zornitza Stark reviewed gene: KCNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31600826, 31513310; Phenotypes: Epileptic encephalopathy, early infantile, 26, MIM# 616056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7888 SYT1 Zornitza Stark Marked gene: SYT1 as ready
Mendeliome v0.7888 SYT1 Zornitza Stark Gene: syt1 has been classified as Green List (High Evidence).
Mendeliome v0.7888 SYT1 Zornitza Stark Phenotypes for gene: SYT1 were changed from to Baker-Gordon syndrome, MIM# 618218; MONDO:0033864
Mendeliome v0.7887 SYT1 Zornitza Stark Publications for gene: SYT1 were set to
Mendeliome v0.7886 SYT1 Zornitza Stark Mode of inheritance for gene: SYT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7885 SYT1 Zornitza Stark reviewed gene: SYT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30107533; Phenotypes: Baker-Gordon syndrome, MIM# 618218, MONDO:0033864; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7885 UBTF Zornitza Stark Marked gene: UBTF as ready
Mendeliome v0.7885 UBTF Zornitza Stark Gene: ubtf has been classified as Green List (High Evidence).
Mendeliome v0.7885 UBTF Zornitza Stark Phenotypes for gene: UBTF were changed from to Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672; MONDO:0044701
Mendeliome v0.7884 UBTF Zornitza Stark Publications for gene: UBTF were set to
Mendeliome v0.7883 UBTF Zornitza Stark Mode of inheritance for gene: UBTF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7882 UBTF Zornitza Stark reviewed gene: UBTF: Rating: GREEN; Mode of pathogenicity: None; Publications: 28777933, 29300972; Phenotypes: Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672, MONDO:0044701; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7882 ZEB2 Zornitza Stark Marked gene: ZEB2 as ready
Mendeliome v0.7882 ZEB2 Zornitza Stark Gene: zeb2 has been classified as Green List (High Evidence).
Mendeliome v0.7882 ZEB2 Zornitza Stark Phenotypes for gene: ZEB2 were changed from Mowat-Wilson syndrome (MIM#235730) to Mowat-Wilson syndrome, MIM# 235730; MONDO:0009341
Mendeliome v0.7881 ZEB2 Zornitza Stark Tag SV/CNV tag was added to gene: ZEB2.
Mendeliome v0.7881 SLC9A6 Zornitza Stark Marked gene: SLC9A6 as ready
Mendeliome v0.7881 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Green List (High Evidence).
Mendeliome v0.7881 SLC9A6 Zornitza Stark Phenotypes for gene: SLC9A6 were changed from to Mental retardation, X-linked syndromic, Christianson type, MIM# 300243; MONDO:0010278
Mendeliome v0.7880 SLC9A6 Zornitza Stark Publications for gene: SLC9A6 were set to
Mendeliome v0.7879 SLC9A6 Zornitza Stark Mode of inheritance for gene: SLC9A6 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7878 SLC9A6 Zornitza Stark reviewed gene: SLC9A6: Rating: GREEN; Mode of pathogenicity: None; Publications: 18342287, 19377476, 25044251, 33278113, 32569089, 31879735; Phenotypes: Mental retardation, X-linked syndromic, Christianson type, MIM# 300243, MONDO:0010278; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7878 RPL3L Zornitza Stark Phenotypes for gene: RPL3L were changed from Neonatal dilated cardiomyopathy to Cardiomyopathy, dilated, 2D, MIM# 619371; Neonatal dilated cardiomyopathy
Mendeliome v0.7877 RPL3L Zornitza Stark reviewed gene: RPL3L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, dilated, 2D, MIM# 619371, Neonatal dilated cardiomyopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7877 SHANK3 Zornitza Stark Publications for gene: SHANK3 were set to 30842224
Mendeliome v0.7876 SHANK3 Zornitza Stark Tag SV/CNV tag was added to gene: SHANK3.
Mendeliome v0.7876 SHANK3 Zornitza Stark reviewed gene: SHANK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 16284256, 17173049, 20186804, 22892527; Phenotypes: Phelan-McDermid syndrome, MIM# 606232; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7876 SHANK3 Zornitza Stark Phenotypes for gene: SHANK3 were changed from Phelan-McDermid syndrome 606232; Rett syndrome; Rett-like phenotypes to Phelan-McDermid syndrome 606232; MONDO:0011652
Mendeliome v0.7875 SATB2 Zornitza Stark Marked gene: SATB2 as ready
Mendeliome v0.7875 SATB2 Zornitza Stark Gene: satb2 has been classified as Green List (High Evidence).
Mendeliome v0.7875 SATB2 Zornitza Stark Phenotypes for gene: SATB2 were changed from to Glass syndrome, MIM# 612313; MONDO:0100147
Mendeliome v0.7874 SATB2 Zornitza Stark Publications for gene: SATB2 were set to
Mendeliome v0.7873 SATB2 Zornitza Stark Mode of inheritance for gene: SATB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7872 SATB2 Zornitza Stark reviewed gene: SATB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29023086, 28151491, 32446642; Phenotypes: Glass syndrome, MIM# 612313, MONDO:0100147; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7872 MEF2C Zornitza Stark Tag SV/CNV tag was added to gene: MEF2C.
Tag 5'UTR tag was added to gene: MEF2C.
Mendeliome v0.7872 MEF2C Zornitza Stark Phenotypes for gene: MEF2C were changed from Chromosome 5q14.3 deletion syndrome, 613443; Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, 613443 to Chromosome 5q14.3 deletion syndrome, 613443; Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, 613443; MONDO:0013266
Mendeliome v0.7871 MEF2C Zornitza Stark Publications for gene: MEF2C were set to
Mendeliome v0.7870 MEF2C Zornitza Stark reviewed gene: MEF2C: Rating: GREEN; Mode of pathogenicity: None; Publications: 19876902, 19471318, 19592390, 19592390, 20513142, 34055696, 34022131; Phenotypes: Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, MIM# 613443, MONDO:0013266 Edit; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7870 MBD5 Zornitza Stark Tag SV/CNV tag was added to gene: MBD5.
Mendeliome v0.7870 MBD5 Zornitza Stark Marked gene: MBD5 as ready
Mendeliome v0.7870 MBD5 Zornitza Stark Gene: mbd5 has been classified as Green List (High Evidence).
Mendeliome v0.7870 MBD5 Zornitza Stark Phenotypes for gene: MBD5 were changed from to Mental retardation, autosomal dominant 1, MIM# 156200; MONDO:0007974
Mendeliome v0.7869 MBD5 Zornitza Stark Publications for gene: MBD5 were set to
Mendeliome v0.7868 MBD5 Zornitza Stark Mode of inheritance for gene: MBD5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7867 MBD5 Zornitza Stark reviewed gene: MBD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 18812405, 21981781, 23708187, 22726846, 33912662; Phenotypes: Mental retardation, autosomal dominant 1, MIM# 156200, MONDO:0007974; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7867 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM#309530 to Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Mendeliome v0.7866 IQSEC2 Zornitza Stark Publications for gene: IQSEC2 were set to 31415821; 20473311; 30842726
Mendeliome v0.7865 IQSEC2 Zornitza Stark reviewed gene: IQSEC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33368194, 20473311, 23674175; Phenotypes: Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656, Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.7865 EEF1A2 Zornitza Stark Phenotypes for gene: EEF1A2 were changed from Epileptic encephalopathy, early infantile, 33, MIM# 616409; Mental retardation, autosomal dominant 38, MIM# 616393 to Mental retardation, autosomal dominant 38, MIM# 616393; MONDO:0014617; Developmental and epileptic encephalopathy 33, MIM# 616409; MONDO:0014625
Mendeliome v0.7864 EEF1A2 Zornitza Stark Publications for gene: EEF1A2 were set to 32160274
Mendeliome v0.7863 EEF1A2 Zornitza Stark reviewed gene: EEF1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24697219, 32196822, 32160274, 32062104, 31893083; Phenotypes: Mental retardation, autosomal dominant 38, MIM# 616393, MONDO:0014617, Developmental and epileptic encephalopathy 33, MIM# 616409, MONDO:0014625; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7863 MASP1 Zornitza Stark Marked gene: MASP1 as ready
Mendeliome v0.7863 MASP1 Zornitza Stark Gene: masp1 has been classified as Green List (High Evidence).
Mendeliome v0.7863 MASP1 Zornitza Stark Phenotypes for gene: MASP1 were changed from to 3MC syndrome 1, MIM# 257920; MONDO:0009770
Mendeliome v0.7862 MASP1 Zornitza Stark Publications for gene: MASP1 were set to
Mendeliome v0.7861 MASP1 Zornitza Stark Mode of inheritance for gene: MASP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7860 MASP1 Zornitza Stark reviewed gene: MASP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26789649, 21258343, 21035106; Phenotypes: 3MC syndrome 1, MIM# 257920, MONDO:0009770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7860 BRPF1 Zornitza Stark Marked gene: BRPF1 as ready
Mendeliome v0.7860 BRPF1 Zornitza Stark Gene: brpf1 has been classified as Green List (High Evidence).
Mendeliome v0.7860 BRPF1 Zornitza Stark Phenotypes for gene: BRPF1 were changed from to Intellectual developmental disorder with dysmorphic facies and ptosis, MIM# 617333; MONDO:0015022
Mendeliome v0.7859 BRPF1 Zornitza Stark Publications for gene: BRPF1 were set to
Mendeliome v0.7858 BRPF1 Zornitza Stark Mode of inheritance for gene: BRPF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7857 BRPF1 Zornitza Stark reviewed gene: BRPF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27939640, 27939639; Phenotypes: Intellectual developmental disorder with dysmorphic facies and ptosis, MIM# 617333, MONDO:0015022; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7857 TRAF7 Zornitza Stark Marked gene: TRAF7 as ready
Mendeliome v0.7857 TRAF7 Zornitza Stark Gene: traf7 has been classified as Green List (High Evidence).
Mendeliome v0.7857 TRAF7 Zornitza Stark Phenotypes for gene: TRAF7 were changed from to Cardiac, facial, and digital anomalies with developmental delay, MIM# 618164
Mendeliome v0.7856 TRAF7 Zornitza Stark Publications for gene: TRAF7 were set to
Mendeliome v0.7855 TRAF7 Zornitza Stark Mode of inheritance for gene: TRAF7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7854 TRAF7 Zornitza Stark reviewed gene: TRAF7: Rating: GREEN; Mode of pathogenicity: None; Publications: 32376980; Phenotypes: Cardiac, facial, and digital anomalies with developmental delay, MIM# 618164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7854 UBE3B Zornitza Stark Marked gene: UBE3B as ready
Mendeliome v0.7854 UBE3B Zornitza Stark Gene: ube3b has been classified as Green List (High Evidence).
Mendeliome v0.7854 UBE3B Zornitza Stark Phenotypes for gene: UBE3B were changed from to Kaufman oculocerebrofacial syndrome, MIM# 244450; MONDO:0009485
Mendeliome v0.7853 UBE3B Zornitza Stark Publications for gene: UBE3B were set to
Mendeliome v0.7852 UBE3B Zornitza Stark Mode of inheritance for gene: UBE3B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7851 UBE3B Zornitza Stark reviewed gene: UBE3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 23200864, 23200864, 34012380, 32949109; Phenotypes: Kaufman oculocerebrofacial syndrome, MIM# 244450, MONDO:0009485; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7851 HSPG2 Zornitza Stark Publications for gene: HSPG2 were set to 16927315
Mendeliome v0.7850 HSPG2 Zornitza Stark reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11101850, 16927315, 11279527; Phenotypes: Schwartz-Jampel syndrome, type 1, MIM# 255800, MONDO:0009717, Dyssegmental dysplasia, Silverman-Handmaker type, MIM# 224410, MONDO:0009140; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7850 HLA-DRB1 Zornitza Stark Marked gene: HLA-DRB1 as ready
Mendeliome v0.7850 HLA-DRB1 Zornitza Stark Gene: hla-drb1 has been classified as Red List (Low Evidence).
Mendeliome v0.7850 HLA-DRB1 Zornitza Stark Classified gene: HLA-DRB1 as Red List (low evidence)
Mendeliome v0.7850 HLA-DRB1 Zornitza Stark Gene: hla-drb1 has been classified as Red List (Low Evidence).
Mendeliome v0.7849 HLA-DRB1 Zornitza Stark reviewed gene: HLA-DRB1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.7849 HLA-DRA Zornitza Stark Marked gene: HLA-DRA as ready
Mendeliome v0.7849 HLA-DRA Zornitza Stark Gene: hla-dra has been classified as Red List (Low Evidence).
Mendeliome v0.7849 HLA-DRA Zornitza Stark Classified gene: HLA-DRA as Red List (low evidence)
Mendeliome v0.7849 HLA-DRA Zornitza Stark Gene: hla-dra has been classified as Red List (Low Evidence).
Mendeliome v0.7848 HLA-DRA Zornitza Stark reviewed gene: HLA-DRA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.7848 HLA-C Zornitza Stark Marked gene: HLA-C as ready
Mendeliome v0.7848 HLA-C Zornitza Stark Gene: hla-c has been classified as Red List (Low Evidence).
Mendeliome v0.7848 HLA-C Zornitza Stark Classified gene: HLA-C as Red List (low evidence)
Mendeliome v0.7848 HLA-C Zornitza Stark Gene: hla-c has been classified as Red List (Low Evidence).
Mendeliome v0.7847 HLA-C Zornitza Stark reviewed gene: HLA-C: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.7847 HLA-B Zornitza Stark Marked gene: HLA-B as ready
Mendeliome v0.7847 HLA-B Zornitza Stark Gene: hla-b has been classified as Red List (Low Evidence).
Mendeliome v0.7847 HLA-B Zornitza Stark Classified gene: HLA-B as Red List (low evidence)
Mendeliome v0.7847 HLA-B Zornitza Stark Gene: hla-b has been classified as Red List (Low Evidence).
Mendeliome v0.7846 HLA-B Zornitza Stark reviewed gene: HLA-B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.7846 HLA-A Zornitza Stark Marked gene: HLA-A as ready
Mendeliome v0.7846 HLA-A Zornitza Stark Gene: hla-a has been classified as Red List (Low Evidence).
Mendeliome v0.7846 HLA-A Zornitza Stark Classified gene: HLA-A as Red List (low evidence)
Mendeliome v0.7846 HLA-A Zornitza Stark Gene: hla-a has been classified as Red List (Low Evidence).
Mendeliome v0.7845 HLA-A Zornitza Stark reviewed gene: HLA-A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.7845 TAF6 Zornitza Stark Marked gene: TAF6 as ready
Mendeliome v0.7845 TAF6 Zornitza Stark Gene: taf6 has been classified as Green List (High Evidence).
Mendeliome v0.7845 TAF6 Zornitza Stark Phenotypes for gene: TAF6 were changed from to Alazami-Yuan syndrome, MIM# 617126
Mendeliome v0.7844 TAF6 Zornitza Stark Publications for gene: TAF6 were set to
Mendeliome v0.7843 TAF6 Zornitza Stark Mode of inheritance for gene: TAF6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7842 TAF6 Zornitza Stark reviewed gene: TAF6: Rating: GREEN; Mode of pathogenicity: None; Publications: 25558065, 25574841, 32030742; Phenotypes: Alazami-Yuan syndrome, MIM# 617126; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7842 ANGPT2 Zornitza Stark Phenotypes for gene: ANGPT2 were changed from Primary lymphoedema to Lymphatic malformation-10, MIM#619369; Primary lymphoedema
Mendeliome v0.7841 ANGPT2 Zornitza Stark edited their review of gene: ANGPT2: Changed phenotypes: Lymphatic malformation-10, MIM#619369, Primary lymphoedema
Mendeliome v0.7841 SLC24A5 Zornitza Stark Marked gene: SLC24A5 as ready
Mendeliome v0.7841 SLC24A5 Zornitza Stark Gene: slc24a5 has been classified as Green List (High Evidence).
Mendeliome v0.7841 SLC24A5 Zornitza Stark Phenotypes for gene: SLC24A5 were changed from to Albinism, oculocutaneous, type VI, MIM# 113750
Mendeliome v0.7840 SLC24A5 Zornitza Stark Publications for gene: SLC24A5 were set to
Mendeliome v0.7839 SLC24A5 Zornitza Stark Mode of inheritance for gene: SLC24A5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7838 SLC24A5 Zornitza Stark reviewed gene: SLC24A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23364476, 23985994, 26491832; Phenotypes: Albinism, oculocutaneous, type VI, MIM# 113750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7838 SLC45A2 Zornitza Stark Marked gene: SLC45A2 as ready
Mendeliome v0.7838 SLC45A2 Zornitza Stark Gene: slc45a2 has been classified as Green List (High Evidence).
Mendeliome v0.7838 SLC45A2 Zornitza Stark Phenotypes for gene: SLC45A2 were changed from to Albinism, oculocutaneous, type IV, MIM# 606574; MONDO:0011683
Mendeliome v0.7837 SLC45A2 Zornitza Stark Publications for gene: SLC45A2 were set to
Mendeliome v0.7836 SLC45A2 Zornitza Stark Mode of inheritance for gene: SLC45A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7835 SLC45A2 Zornitza Stark reviewed gene: SLC45A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11574907, 14722913, 14961451; Phenotypes: Albinism, oculocutaneous, type IV, MIM# 606574, MONDO:0011683; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7835 TYR Zornitza Stark Marked gene: TYR as ready
Mendeliome v0.7835 TYR Zornitza Stark Gene: tyr has been classified as Green List (High Evidence).
Mendeliome v0.7835 TYR Zornitza Stark Phenotypes for gene: TYR were changed from to Albinism, oculocutaneous, type IA, MIM# 203100; MONDO:0008745; Albinism, oculocutaneous, type IB, MIM# 606952
Mendeliome v0.7834 TYR Zornitza Stark Mode of inheritance for gene: TYR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7833 TYR Zornitza Stark reviewed gene: TYR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Albinism, oculocutaneous, type IA, MIM# 203100, MONDO:0008745, Albinism, oculocutaneous, type IB, MIM# 606952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7833 TYRP1 Zornitza Stark Marked gene: TYRP1 as ready
Mendeliome v0.7833 TYRP1 Zornitza Stark Gene: tyrp1 has been classified as Green List (High Evidence).
Mendeliome v0.7833 TYRP1 Zornitza Stark Phenotypes for gene: TYRP1 were changed from to Albinism, oculocutaneous, type III, MIM# 203290; MONDO:0008747
Mendeliome v0.7832 TYRP1 Zornitza Stark Publications for gene: TYRP1 were set to
Mendeliome v0.7831 TYRP1 Zornitza Stark Mode of inheritance for gene: TYRP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7830 TYRP1 Zornitza Stark reviewed gene: TYRP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9345097; Phenotypes: Albinism, oculocutaneous, type III, MIM# 203290, MONDO:0008747; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7830 MC1R Zornitza Stark Marked gene: MC1R as ready
Mendeliome v0.7830 MC1R Zornitza Stark Gene: mc1r has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7830 MC1R Zornitza Stark Phenotypes for gene: MC1R were changed from to {Albinism, oculocutaneous, type II, modifier of}, MIM# 203200
Mendeliome v0.7829 MC1R Zornitza Stark Publications for gene: MC1R were set to
Mendeliome v0.7828 MC1R Zornitza Stark Mode of inheritance for gene: MC1R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7827 MC1R Zornitza Stark Classified gene: MC1R as Amber List (moderate evidence)
Mendeliome v0.7827 MC1R Zornitza Stark Gene: mc1r has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7826 MC1R Zornitza Stark reviewed gene: MC1R: Rating: AMBER; Mode of pathogenicity: None; Publications: 12876664; Phenotypes: {Albinism, oculocutaneous, type II, modifier of}, MIM# 203200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7826 LRMDA Zornitza Stark Marked gene: LRMDA as ready
Mendeliome v0.7826 LRMDA Zornitza Stark Gene: lrmda has been classified as Green List (High Evidence).
Mendeliome v0.7826 LRMDA Zornitza Stark Phenotypes for gene: LRMDA were changed from to Albinism, oculocutaneous, type VII, MIM# 615179; MONDO:0014070
Mendeliome v0.7825 LRMDA Zornitza Stark Publications for gene: LRMDA were set to
Mendeliome v0.7824 LRMDA Zornitza Stark Mode of inheritance for gene: LRMDA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7823 LRMDA Zornitza Stark reviewed gene: LRMDA: Rating: GREEN; Mode of pathogenicity: None; Publications: 23395477; Phenotypes: Albinism, oculocutaneous, type VII, MIM# 615179, MONDO:0014070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7823 SERPINF2 Zornitza Stark Marked gene: SERPINF2 as ready
Mendeliome v0.7823 SERPINF2 Zornitza Stark Gene: serpinf2 has been classified as Green List (High Evidence).
Mendeliome v0.7823 SERPINF2 Zornitza Stark Phenotypes for gene: SERPINF2 were changed from to Alpha-2-plasmin inhibitor deficiency, MIM# 262850
Mendeliome v0.7822 SERPINF2 Zornitza Stark Publications for gene: SERPINF2 were set to
Mendeliome v0.7821 SERPINF2 Zornitza Stark Mode of inheritance for gene: SERPINF2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7820 SERPINF2 Zornitza Stark reviewed gene: SERPINF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 2572590, 10583218, 31441040, 31282989, 29656168; Phenotypes: Alpha-2-plasmin inhibitor deficiency, MIM# 262850; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7820 SERPINE1 Zornitza Stark Marked gene: SERPINE1 as ready
Mendeliome v0.7820 SERPINE1 Zornitza Stark Gene: serpine1 has been classified as Green List (High Evidence).
Mendeliome v0.7820 SERPINE1 Zornitza Stark Phenotypes for gene: SERPINE1 were changed from to Plasminogen activator inhibitor-1 deficiency, MIM# 613329
Mendeliome v0.7819 SERPINE1 Zornitza Stark Publications for gene: SERPINE1 were set to
Mendeliome v0.7818 SERPINE1 Zornitza Stark Mode of inheritance for gene: SERPINE1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.7817 SERPINE1 Zornitza Stark reviewed gene: SERPINE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9207454, 15650551; Phenotypes: Plasminogen activator inhibitor-1 deficiency, MIM# 613329; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.7817 TBXA2R Zornitza Stark Marked gene: TBXA2R as ready
Mendeliome v0.7817 TBXA2R Zornitza Stark Gene: tbxa2r has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7817 TBXA2R Zornitza Stark Phenotypes for gene: TBXA2R were changed from to {Bleeding disorder, platelet-type, 13, susceptibility to}, MIM# 614009
Mendeliome v0.7816 TBXA2R Zornitza Stark Publications for gene: TBXA2R were set to
Mendeliome v0.7815 TBXA2R Zornitza Stark Mode of inheritance for gene: TBXA2R was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7814 TBXA2R Zornitza Stark Classified gene: TBXA2R as Amber List (moderate evidence)
Mendeliome v0.7814 TBXA2R Zornitza Stark Gene: tbxa2r has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7813 TBXA2R Zornitza Stark reviewed gene: TBXA2R: Rating: AMBER; Mode of pathogenicity: None; Publications: 7929844, 19828703, 22517902; Phenotypes: {Bleeding disorder, platelet-type, 13, susceptibility to}, MIM# 614009; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7813 P2RY12 Zornitza Stark Marked gene: P2RY12 as ready
Mendeliome v0.7813 P2RY12 Zornitza Stark Gene: p2ry12 has been classified as Green List (High Evidence).
Mendeliome v0.7813 P2RY12 Zornitza Stark Phenotypes for gene: P2RY12 were changed from to Bleeding disorder, platelet-type, 8, MIM# 609821; MONDO:0012354
Mendeliome v0.7812 P2RY12 Zornitza Stark Publications for gene: P2RY12 were set to
Mendeliome v0.7811 P2RY12 Zornitza Stark Mode of inheritance for gene: P2RY12 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7810 P2RY12 Zornitza Stark reviewed gene: P2RY12: Rating: GREEN; Mode of pathogenicity: None; Publications: 11196645, 12578987, 29117459, 19237732; Phenotypes: Bleeding disorder, platelet-type, 8, MIM# 609821, MONDO:0012354; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7810 MCFD2 Zornitza Stark Marked gene: MCFD2 as ready
Mendeliome v0.7810 MCFD2 Zornitza Stark Gene: mcfd2 has been classified as Green List (High Evidence).
Mendeliome v0.7810 MCFD2 Zornitza Stark Phenotypes for gene: MCFD2 were changed from to Factor V and factor VIII, combined deficiency of, MIM# 613625; MONDO:0013331
Mendeliome v0.7809 MCFD2 Zornitza Stark Publications for gene: MCFD2 were set to
Mendeliome v0.7808 MCFD2 Zornitza Stark Mode of inheritance for gene: MCFD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7807 MCFD2 Zornitza Stark reviewed gene: MCFD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12717434, 16304051, 18391077; Phenotypes: Factor V and factor VIII, combined deficiency of, MIM# 613625, MONDO:0013331; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7807 LMAN1 Zornitza Stark Marked gene: LMAN1 as ready
Mendeliome v0.7807 LMAN1 Zornitza Stark Gene: lman1 has been classified as Green List (High Evidence).
Mendeliome v0.7807 LMAN1 Zornitza Stark Phenotypes for gene: LMAN1 were changed from to Combined factor V and VIII deficiency, MIM# 227300; MONDO:0009206
Mendeliome v0.7806 LMAN1 Zornitza Stark Publications for gene: LMAN1 were set to
Mendeliome v0.7805 LMAN1 Zornitza Stark Mode of inheritance for gene: LMAN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7804 LMAN1 Zornitza Stark reviewed gene: LMAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9546392, 16304051; Phenotypes: Combined factor V and VIII deficiency, MIM# 227300, MONDO:0009206; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7804 ITGA2B Zornitza Stark Marked gene: ITGA2B as ready
Mendeliome v0.7804 ITGA2B Zornitza Stark Gene: itga2b has been classified as Green List (High Evidence).
Mendeliome v0.7804 ITGA2B Zornitza Stark Phenotypes for gene: ITGA2B were changed from to Bleeding disorder, platelet-type, 16, MIM# 187800; MONDO:000855; Glanzmann thrombasthaenia 1, MIM# 273800
Mendeliome v0.7803 ITGA2B Zornitza Stark Publications for gene: ITGA2B were set to
Mendeliome v0.7802 ITGA2B Zornitza Stark Mode of inheritance for gene: ITGA2B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7801 ITGA2B Zornitza Stark reviewed gene: ITGA2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 1638023, 21454453, 8282784, 16463284; Phenotypes: Bleeding disorder, platelet-type, 16, MIM# 187800, MONDO:000855, Glanzmann thrombasthaenia 1, MIM# 273800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7801 LMOD1 Zornitza Stark Marked gene: LMOD1 as ready
Mendeliome v0.7801 LMOD1 Zornitza Stark Gene: lmod1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7801 LMOD1 Zornitza Stark Phenotypes for gene: LMOD1 were changed from to Megacystis-microcolon-intestinal hypoperistalsis syndrome 3, MIM# 619362
Mendeliome v0.7800 LMOD1 Zornitza Stark Publications for gene: LMOD1 were set to
Mendeliome v0.7799 LMOD1 Zornitza Stark Mode of inheritance for gene: LMOD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7798 LMOD1 Zornitza Stark Classified gene: LMOD1 as Amber List (moderate evidence)
Mendeliome v0.7798 LMOD1 Zornitza Stark Gene: lmod1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7797 LMOD1 Zornitza Stark reviewed gene: LMOD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28292896; Phenotypes: Megacystis-microcolon-intestinal hypoperistalsis syndrome 3, MIM# 619362; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7797 POU4F1 Bryony Thompson Marked gene: POU4F1 as ready
Mendeliome v0.7797 POU4F1 Bryony Thompson Gene: pou4f1 has been classified as Green List (High Evidence).
Mendeliome v0.7797 POU4F1 Bryony Thompson Classified gene: POU4F1 as Green List (high evidence)
Mendeliome v0.7797 POU4F1 Bryony Thompson Gene: pou4f1 has been classified as Green List (High Evidence).
Mendeliome v0.7796 POU4F1 Bryony Thompson gene: POU4F1 was added
gene: POU4F1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POU4F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POU4F1 were set to 33783914; 8876243
Phenotypes for gene: POU4F1 were set to Ataxia; intention tremor; hypotonia
Review for gene: POU4F1 was set to GREEN
Added comment: 4 unrelated probands presenting with paediatric onset ataxia, intention tremor, and hypotonia, with de novo loss of function variants, and supporting null mouse model.
Sources: Literature
Mendeliome v0.7795 HPS6 Zornitza Stark Marked gene: HPS6 as ready
Mendeliome v0.7795 HPS6 Zornitza Stark Gene: hps6 has been classified as Green List (High Evidence).
Mendeliome v0.7795 HPS6 Zornitza Stark Phenotypes for gene: HPS6 were changed from to Hermansky-Pudlak syndrome 6, MIM# 614075; MONDO:0013558
Mendeliome v0.7794 HPS6 Zornitza Stark Publications for gene: HPS6 were set to
Mendeliome v0.7793 HPS6 Zornitza Stark Mode of inheritance for gene: HPS6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7792 HPS6 Zornitza Stark reviewed gene: HPS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 12548288, 17041891, 19843503; Phenotypes: Hermansky-Pudlak syndrome 6, MIM# 614075, MONDO:0013558; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7792 HPS4 Zornitza Stark Marked gene: HPS4 as ready
Mendeliome v0.7792 HPS4 Zornitza Stark Gene: hps4 has been classified as Green List (High Evidence).
Mendeliome v0.7792 HPS4 Zornitza Stark Publications for gene: HPS4 were set to
Mendeliome v0.7791 HPS4 Zornitza Stark Phenotypes for gene: HPS4 were changed from to Hermansky-Pudlak syndrome 4, MIM# 614073; MONDO:0013556
Mendeliome v0.7790 HPS4 Zornitza Stark Mode of inheritance for gene: HPS4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7789 HPS4 Zornitza Stark reviewed gene: HPS4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11836498, 12664304; Phenotypes: Hermansky-Pudlak syndrome 4, MIM# 614073, MONDO:0013556; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7789 HPS3 Zornitza Stark Marked gene: HPS3 as ready
Mendeliome v0.7789 HPS3 Zornitza Stark Gene: hps3 has been classified as Green List (High Evidence).
Mendeliome v0.7789 HPS3 Zornitza Stark Phenotypes for gene: HPS3 were changed from to Hermansky-Pudlak syndrome 3, MIM# 614072; MONDO:0013555
Mendeliome v0.7788 HPS3 Zornitza Stark Publications for gene: HPS3 were set to
Mendeliome v0.7787 HPS3 Zornitza Stark Mode of inheritance for gene: HPS3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7786 HPS3 Zornitza Stark reviewed gene: HPS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 11455388, 31880485, 31621111, 30990103; Phenotypes: Hermansky-Pudlak syndrome 3, MIM# 614072, MONDO:0013555; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7786 HPS1 Zornitza Stark Marked gene: HPS1 as ready
Mendeliome v0.7786 HPS1 Zornitza Stark Gene: hps1 has been classified as Green List (High Evidence).
Mendeliome v0.7786 HPS1 Zornitza Stark Phenotypes for gene: HPS1 were changed from to Hermansky-Pudlak syndrome 1, MIM# 203300; MONDO:0008748
Mendeliome v0.7785 HPS1 Zornitza Stark Publications for gene: HPS1 were set to
Mendeliome v0.7784 HPS1 Zornitza Stark Mode of inheritance for gene: HPS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7783 HPS1 Zornitza Stark reviewed gene: HPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9497254; Phenotypes: Hermansky-Pudlak syndrome 1, MIM# 203300, MONDO:0008748; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7783 GP9 Zornitza Stark Marked gene: GP9 as ready
Mendeliome v0.7783 GP9 Zornitza Stark Gene: gp9 has been classified as Green List (High Evidence).
Mendeliome v0.7783 GP9 Zornitza Stark Phenotypes for gene: GP9 were changed from to Bernard-Soulier syndrome, type C, MIM# 231200
Mendeliome v0.7782 GP9 Zornitza Stark Publications for gene: GP9 were set to
Mendeliome v0.7781 GP9 Zornitza Stark Mode of inheritance for gene: GP9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7780 GP9 Zornitza Stark reviewed gene: GP9: Rating: GREEN; Mode of pathogenicity: None; Publications: 8049428, 33553065, 32030720, 31484196; Phenotypes: Bernard-Soulier syndrome, type C, MIM# 231200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7780 GP6 Zornitza Stark Marked gene: GP6 as ready
Mendeliome v0.7780 GP6 Zornitza Stark Gene: gp6 has been classified as Green List (High Evidence).
Mendeliome v0.7780 GP6 Zornitza Stark Phenotypes for gene: GP6 were changed from to Bleeding disorder, platelet-type, 11, MIM# 614201; MONDO:0013623
Mendeliome v0.7779 GP6 Zornitza Stark Publications for gene: GP6 were set to
Mendeliome v0.7778 GP6 Zornitza Stark Mode of inheritance for gene: GP6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7777 GP6 Zornitza Stark reviewed gene: GP6: Rating: GREEN; Mode of pathogenicity: None; Publications: 19549989, 19552682, 23815599; Phenotypes: Bleeding disorder, platelet-type, 11, MIM# 614201, MONDO:0013623; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7777 GP1BB Zornitza Stark Marked gene: GP1BB as ready
Mendeliome v0.7777 GP1BB Zornitza Stark Gene: gp1bb has been classified as Green List (High Evidence).
Mendeliome v0.7777 GP1BB Zornitza Stark Phenotypes for gene: GP1BB were changed from to Bernard-Soulier syndrome, type B, MIM# 231200; Macrothrombocytopaenia
Mendeliome v0.7776 GP1BB Zornitza Stark Publications for gene: GP1BB were set to
Mendeliome v0.7775 GP1BB Zornitza Stark Mode of inheritance for gene: GP1BB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7774 GP1BB Zornitza Stark reviewed gene: GP1BB: Rating: GREEN; Mode of pathogenicity: None; Publications: 8703016, 9116284, 10887115, 33813986, 33657022, 33216977, 31997307, 1730088, 11222377; Phenotypes: Bernard-Soulier syndrome, type B, MIM# 231200, Macrothrombocytopaenia; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7774 CREB3L3 Zornitza Stark Marked gene: CREB3L3 as ready
Mendeliome v0.7774 CREB3L3 Zornitza Stark Gene: creb3l3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7774 CREB3L3 Zornitza Stark Phenotypes for gene: CREB3L3 were changed from Hyperlipidaemia; hypertriglyceridemia to Hypertriglyceridaemia-2, MIM#619324
Mendeliome v0.7773 CREB3L3 Zornitza Stark reviewed gene: CREB3L3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertriglyceridaemia-2, MIM#619324; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7773 PSMC3 Zornitza Stark Phenotypes for gene: PSMC3 were changed from Deafness; cataract to Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354
Mendeliome v0.7772 PSMC3 Zornitza Stark edited their review of gene: PSMC3: Changed phenotypes: Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354
Mendeliome v0.7772 PSMC3 Zornitza Stark edited their review of gene: PSMC3: Changed phenotypes: Feafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354
Mendeliome v0.7772 SCNN1B Zornitza Stark Marked gene: SCNN1B as ready
Mendeliome v0.7772 SCNN1B Zornitza Stark Gene: scnn1b has been classified as Green List (High Evidence).
Mendeliome v0.7772 SCNN1B Zornitza Stark Phenotypes for gene: SCNN1B were changed from to Liddle syndrome 1, MIM# 177200; Pseudohypoaldosteronism, type I, MIM# 264350; Bronchiectasis with or without elevated sweat chloride 1 (MIM#211400)
Mendeliome v0.7771 SCNN1B Zornitza Stark Mode of inheritance for gene: SCNN1B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7770 SCNN1B Zornitza Stark reviewed gene: SCNN1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Liddle syndrome 1, MIM# 177200, Pseudohypoaldosteronism, type I, MIM# 264350, Bronchiectasis with or without elevated sweat chloride 1 (MIM#211400); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7770 FGB Zornitza Stark Marked gene: FGB as ready
Mendeliome v0.7770 FGB Zornitza Stark Gene: fgb has been classified as Green List (High Evidence).
Mendeliome v0.7770 FGB Zornitza Stark Phenotypes for gene: FGB were changed from to Afibrinogenaemia, congenital, MIM# 202400; Hypofibrinogenaemia, congenital, MIM# 202400; Dysfibrinogenaemia, congenital, MIM# 616004
Mendeliome v0.7769 FGB Zornitza Stark Publications for gene: FGB were set to
Mendeliome v0.7768 FGB Zornitza Stark Mode of inheritance for gene: FGB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7767 FGB Zornitza Stark changed review comment from: Inherited disorders of fibrinogen affect either the quantity (afibrinogenaemia and hypofibrinogenaemia) or the quality (dysfibrinogenemia) of the circulating fibrinogen or both.

Afibrinogenaemia is characterized by the complete absence of immunoreactive fibrinogen. Bleeding due to afibrinogenaemia usually manifests in the neonatal period, with 85% of cases presenting umbilical cord bleeding, but a later age of onst is not unusual. Bleeding may occur in the skin, gastrointestinal tract, genitourinary tract, or the central nervous system, with intracranial haemorrhage being reported as the major cause of death. Patients are susceptible to spontaneous rupture of the spleen. First-trimester pregnancy loss is common. Both arterial and venous thromboembolic complications have been reported. Hypofibrinogenaemia is a milder disorder. Well established gene-disease association.; to: Inherited disorders of fibrinogen affect either the quantity (afibrinogenaemia and hypofibrinogenaemia) or the quality (dysfibrinogenemia) of the circulating fibrinogen or both.

Afibrinogenaemia is characterized by the complete absence of immunoreactive fibrinogen. Bleeding due to afibrinogenaemia usually manifests in the neonatal period, with 85% of cases presenting umbilical cord bleeding, but a later age of onst is not unusual. Bleeding may occur in the skin, gastrointestinal tract, genitourinary tract, or the central nervous system, with intracranial haemorrhage being reported as the major cause of death. Patients are susceptible to spontaneous rupture of the spleen. First-trimester pregnancy loss is common. Both arterial and venous thromboembolic complications have been reported. Hypofibrinogenaemia is a milder disorder.

Well established gene-disease association.
Mendeliome v0.7767 FGB Zornitza Stark reviewed gene: FGB: Rating: GREEN; Mode of pathogenicity: None; Publications: 12393540, 16195396; Phenotypes: Afibrinogenaemia, congenital, MIM# 202400, Hypofibrinogenaemia, congenital, MIM# 202400, Dysfibrinogenaemia, congenital, MIM# 616004; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7767 F9 Zornitza Stark Marked gene: F9 as ready
Mendeliome v0.7767 F9 Zornitza Stark Gene: f9 has been classified as Green List (High Evidence).
Mendeliome v0.7767 F9 Zornitza Stark Phenotypes for gene: F9 were changed from to Haemophilia B, MIM# 306900; Thrombophilia, X-linked, due to factor IX defect, MIM# 300807
Mendeliome v0.7766 F9 Zornitza Stark Publications for gene: F9 were set to
Mendeliome v0.7765 F9 Zornitza Stark Mode of inheritance for gene: F9 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7764 F9 Zornitza Stark reviewed gene: F9: Rating: GREEN; Mode of pathogenicity: None; Publications: 19846852, 34015304, 33656538; Phenotypes: Haemophilia B, MIM# 306900, Thrombophilia, X-linked, due to factor IX defect, MIM# 300807; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7764 F8 Zornitza Stark Marked gene: F8 as ready
Mendeliome v0.7764 F8 Zornitza Stark Gene: f8 has been classified as Green List (High Evidence).
Mendeliome v0.7764 F8 Zornitza Stark Phenotypes for gene: F8 were changed from to Haemophilia A, MIM# 306700; MONDO:0010602
Mendeliome v0.7763 F8 Zornitza Stark Publications for gene: F8 were set to
Mendeliome v0.7762 F8 Zornitza Stark Mode of inheritance for gene: F8 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7761 F8 Zornitza Stark reviewed gene: F8: Rating: GREEN; Mode of pathogenicity: None; Publications: 2986011, 3097553; Phenotypes: Haemophilia A, MIM# 306700, MONDO:0010602; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7761 F7 Zornitza Stark Marked gene: F7 as ready
Mendeliome v0.7761 F7 Zornitza Stark Gene: f7 has been classified as Green List (High Evidence).
Mendeliome v0.7761 F7 Zornitza Stark Phenotypes for gene: F7 were changed from to Factor VII deficiency, MIM# 227500; MONDO:0009211
Mendeliome v0.7760 F7 Zornitza Stark Publications for gene: F7 were set to
Mendeliome v0.7759 F7 Zornitza Stark Mode of inheritance for gene: F7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7758 F7 Zornitza Stark reviewed gene: F7: Rating: GREEN; Mode of pathogenicity: None; Publications: 12181036; Phenotypes: Factor VII deficiency, MIM# 227500, MONDO:0009211; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7758 F5 Zornitza Stark Marked gene: F5 as ready
Mendeliome v0.7758 F5 Zornitza Stark Gene: f5 has been classified as Green List (High Evidence).
Mendeliome v0.7758 F5 Zornitza Stark Phenotypes for gene: F5 were changed from to Factor V deficiency, MIM# 227400; MONDO:0009210; Thrombophilia due to activated protein C resistance, MIM# 188055; MONDO:0008560; {Thrombophilia, susceptibility to, due to factor V Leiden}, MIM# 188055
Mendeliome v0.7757 F5 Zornitza Stark Mode of inheritance for gene: F5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7756 F5 Zornitza Stark reviewed gene: F5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Factor V deficiency, MIM# 227400, MONDO:0009210, Thrombophilia due to activated protein C resistance, MIM# 188055, MONDO:0008560, {Thrombophilia, susceptibility to, due to factor V Leiden}, MIM# 188055; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7756 F13A1 Zornitza Stark Marked gene: F13A1 as ready
Mendeliome v0.7756 F13A1 Zornitza Stark Gene: f13a1 has been classified as Green List (High Evidence).
Mendeliome v0.7756 F13A1 Zornitza Stark Phenotypes for gene: F13A1 were changed from to Factor XIIIA deficiency, MIM# 613225; MONDO:0013187
Mendeliome v0.7755 F13A1 Zornitza Stark Publications for gene: F13A1 were set to
Mendeliome v0.7754 F13A1 Zornitza Stark Mode of inheritance for gene: F13A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7753 F13A1 Zornitza Stark reviewed gene: F13A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 1644910, 7727776, 10027709, 33802692, 32060721; Phenotypes: Factor XIIIA deficiency, MIM# 613225, MONDO:0013187; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7753 F10 Zornitza Stark Marked gene: F10 as ready
Mendeliome v0.7753 F10 Zornitza Stark Gene: f10 has been classified as Green List (High Evidence).
Mendeliome v0.7753 F10 Zornitza Stark Phenotypes for gene: F10 were changed from to Factor X deficiency, MIM# 227600; MONDO:0009212
Mendeliome v0.7752 F10 Zornitza Stark Publications for gene: F10 were set to
Mendeliome v0.7751 F10 Zornitza Stark Mode of inheritance for gene: F10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7750 F10 Zornitza Stark Deleted their comment
Mendeliome v0.7750 F10 Zornitza Stark commented on gene: F10: Factor X deficiency shows variable phenotypic severity. Affected individuals can manifest prolonged nasal and mucosal haemorrhage, menorrhagia, haematuria, and occasionally haemarthrosis. More than 20 unrelated families reported.
Mendeliome v0.7750 F10 Zornitza Stark reviewed gene: F10: Rating: GREEN; Mode of pathogenicity: None; Publications: 2790181, 2567188, 10746568, 12028042; Phenotypes: Factor X deficiency, MIM# 227600, MONDO:0009212; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7750 MCM7 Zornitza Stark Marked gene: MCM7 as ready
Mendeliome v0.7750 MCM7 Zornitza Stark Gene: mcm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7750 MCM7 Zornitza Stark Classified gene: MCM7 as Amber List (moderate evidence)
Mendeliome v0.7750 MCM7 Zornitza Stark Gene: mcm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7749 MCM7 Arina Puzriakova gene: MCM7 was added
gene: MCM7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MCM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM7 were set to 33654309; 34059554
Phenotypes for gene: MCM7 were set to Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency
Review for gene: MCM7 was set to AMBER
Added comment: MCM7 is a component of the MCM complex, a DNA helicase which is essential for DNA replication. Other components have been linked to disease with phenotypes including microcephaly and ID. MCM7 is not associated with any phenotype in OMIM or G2P at present.
------
Currently there are 3 unrelated pedigrees in literature with different biallelic MCM7 variants associated with disease (see below). Although there is some functional data in support of variant-level deleteriousness or gene-level pathogenicity, the clinical gestalt is very different between the 3 families.

- PMID: 33654309 (2021) - Two unrelated individuals with different compound het variants in MCM7 but disparate clinical features. One patient had typical Meier-Gorlin syndrome (including growth retardation, microcephaly, congenital lung emphysema, absent breast development, microtia, facial dysmorphism) whereas the second case had a multi-system disorder with neonatal progeroid appearance, lipodystrophy and adrenal insufficiency. While small at birth, the second patient did not demonstrate reduced stature or microcephaly at age 14.5 years. Both individuals had normal neurodevelopment.
Functional studies using patient-derived fibroblasts demonstrate that the identified MCM7 variants were deleterious at either transcript or protein levels and through interfering with MCM complex formation, impact efficiency of S phase progression.

- PMID: 34059554 (2021) - Homozygous missense variant identified in three affected individuals from a consanguineous family with severe primary microcephaly, severe ID and behavioural abnormalities. Knockdown of Mcm7 in mouse neuroblastoma cells lead to reduced cell viability and proliferation with increased apoptosis, which were rescued by overexpression of wild-type but not mutant MCM7.
Sources: Literature
Mendeliome v0.7749 DTNBP1 Zornitza Stark Marked gene: DTNBP1 as ready
Mendeliome v0.7749 DTNBP1 Zornitza Stark Gene: dtnbp1 has been classified as Green List (High Evidence).
Mendeliome v0.7749 DTNBP1 Zornitza Stark Phenotypes for gene: DTNBP1 were changed from to Hermansky-Pudlak syndrome 7, MIM# 614076; MONDO:0013559
Mendeliome v0.7748 DTNBP1 Zornitza Stark Publications for gene: DTNBP1 were set to
Mendeliome v0.7747 DTNBP1 Zornitza Stark Mode of inheritance for gene: DTNBP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7746 DTNBP1 Zornitza Stark reviewed gene: DTNBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12923531, 23364359, 28259707, 30990103; Phenotypes: Hermansky-Pudlak syndrome 7, MIM# 614076, MONDO:0013559; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7746 BLOC1S3 Zornitza Stark Marked gene: BLOC1S3 as ready
Mendeliome v0.7746 BLOC1S3 Zornitza Stark Gene: bloc1s3 has been classified as Green List (High Evidence).
Mendeliome v0.7746 BLOC1S3 Zornitza Stark Phenotypes for gene: BLOC1S3 were changed from to Hermansky-Pudlak syndrome 8, MIM# 614077; MONDO:0013560
Mendeliome v0.7745 BLOC1S3 Zornitza Stark Publications for gene: BLOC1S3 were set to
Mendeliome v0.7744 BLOC1S3 Zornitza Stark Mode of inheritance for gene: BLOC1S3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7743 BLOC1S3 Zornitza Stark reviewed gene: BLOC1S3: Rating: GREEN; Mode of pathogenicity: None; Publications: 16385460, 22709368, 32687635; Phenotypes: Hermansky-Pudlak syndrome 8, MIM# 614077, MONDO:0013560; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7743 AP3B1 Zornitza Stark Marked gene: AP3B1 as ready
Mendeliome v0.7743 AP3B1 Zornitza Stark Gene: ap3b1 has been classified as Green List (High Evidence).
Mendeliome v0.7743 AP3B1 Zornitza Stark Phenotypes for gene: AP3B1 were changed from to Hermansky-Pudlak syndrome 2, MIM# 608233; MONDO:0011997
Mendeliome v0.7742 AP3B1 Zornitza Stark Publications for gene: AP3B1 were set to
Mendeliome v0.7741 AP3B1 Zornitza Stark Mode of inheritance for gene: AP3B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7740 AP3B1 Zornitza Stark reviewed gene: AP3B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10024875, 11809908, 14566336; Phenotypes: Hermansky-Pudlak syndrome 2, MIM# 608233, MONDO:0011997; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7740 LHCGR Zornitza Stark Marked gene: LHCGR as ready
Mendeliome v0.7740 LHCGR Zornitza Stark Gene: lhcgr has been classified as Green List (High Evidence).
Mendeliome v0.7740 LHCGR Zornitza Stark Phenotypes for gene: LHCGR were changed from to Luteinizing hormone resistance, female, (MIM#238320); Leydig cell hypoplasia with pseudohermaphroditism, (MIM#238320); Leydig cell hypoplasia with hypergonadotropic hypogonadism, (MIM#238320); Precocious puberty, male, (MIM#176410)
Mendeliome v0.7739 LHCGR Zornitza Stark Publications for gene: LHCGR were set to
Mendeliome v0.7738 LHCGR Zornitza Stark Mode of inheritance for gene: LHCGR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7737 NEB Zornitza Stark Publications for gene: NEB were set to 25205138
Mendeliome v0.7736 NEB Zornitza Stark Phenotypes for gene: NEB were changed from Nemaline myopathy 2, autosomal recessive 256030 to Nemaline myopathy 2, autosomal recessive 256030; MONDO:0009725; Arthrogryposis multiplex congenita 6, MIM# 619334
Mendeliome v0.7735 NEB Zornitza Stark reviewed gene: NEB: Rating: GREEN; Mode of pathogenicity: None; Publications: 10051637, 22367672, 26578207, 33376055; Phenotypes: Arthrogryposis multiplex congenita 6, MIM# 619334; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7735 LHCGR Ain Roesley reviewed gene: LHCGR: Rating: GREEN; Mode of pathogenicity: None; Publications: 11041448; Phenotypes: Luteinizing hormone resistance, female, (MIM#238320), Leydig cell hypoplasia with pseudohermaphroditism, (MIM#238320), Leydig cell hypoplasia with hypergonadotropic hypogonadism, (MIM#238320), Precocious puberty, male, (MIM#176410); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7735 GEMIN5 Zornitza Stark Marked gene: GEMIN5 as ready
Mendeliome v0.7735 GEMIN5 Zornitza Stark Gene: gemin5 has been classified as Green List (High Evidence).
Mendeliome v0.7735 GEMIN5 Zornitza Stark Classified gene: GEMIN5 as Green List (high evidence)
Mendeliome v0.7735 GEMIN5 Zornitza Stark Gene: gemin5 has been classified as Green List (High Evidence).
Mendeliome v0.7734 GEMIN5 Zornitza Stark gene: GEMIN5 was added
gene: GEMIN5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GEMIN5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GEMIN5 were set to 33963192
Phenotypes for gene: GEMIN5 were set to Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction, MIM# 619333
Review for gene: GEMIN5 was set to GREEN
Added comment: Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (NEDCAM) is an autosomal recessive disorder characterized by global developmental delay with prominent motor abnormalities, mainly axial hypotonia, gait ataxia, and appendicular spasticity. Affected individuals have cognitive impairment and speech delay; brain imaging shows cerebellar atrophy. 30 individuals from 22 unrelated families reported.
Sources: Literature
Mendeliome v0.7733 ANO6 Zornitza Stark Marked gene: ANO6 as ready
Mendeliome v0.7733 ANO6 Zornitza Stark Gene: ano6 has been classified as Green List (High Evidence).
Mendeliome v0.7733 ANO6 Zornitza Stark Phenotypes for gene: ANO6 were changed from to Scott syndrome, MIM# 262890; MONDO:0009885
Mendeliome v0.7732 ANO6 Zornitza Stark Publications for gene: ANO6 were set to
Mendeliome v0.7731 ANO6 Zornitza Stark Mode of inheritance for gene: ANO6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7730 ANO6 Zornitza Stark reviewed gene: ANO6: Rating: GREEN; Mode of pathogenicity: None; Publications: 21107324, 11895776, 27879994, 27634832; Phenotypes: Scott syndrome, MIM# 262890, MONDO:0009885; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7730 KLHL3 Zornitza Stark Marked gene: KLHL3 as ready
Mendeliome v0.7730 KLHL3 Zornitza Stark Gene: klhl3 has been classified as Green List (High Evidence).
Mendeliome v0.7730 KLHL3 Zornitza Stark Phenotypes for gene: KLHL3 were changed from to Pseudohypoaldosteronism, type IID, MIM# 614495
Mendeliome v0.7729 KLHL3 Zornitza Stark Publications for gene: KLHL3 were set to
Mendeliome v0.7728 KLHL3 Zornitza Stark Mode of inheritance for gene: KLHL3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7727 KLHL3 Zornitza Stark reviewed gene: KLHL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22266938, 22406640, 24821705, 34022862, 32462939; Phenotypes: Pseudohypoaldosteronism, type IID, MIM# 614495; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7727 KCNJ5 Zornitza Stark Marked gene: KCNJ5 as ready
Mendeliome v0.7727 KCNJ5 Zornitza Stark Gene: kcnj5 has been classified as Green List (High Evidence).
Mendeliome v0.7727 KCNJ5 Zornitza Stark Classified gene: KCNJ5 as Green List (high evidence)
Mendeliome v0.7727 KCNJ5 Zornitza Stark Gene: kcnj5 has been classified as Green List (High Evidence).
Mendeliome v0.7726 KCNJ5 Zornitza Stark gene: KCNJ5 was added
gene: KCNJ5 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KCNJ5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ5 were set to 21311022; 22203740; 24420545; 24574546
Phenotypes for gene: KCNJ5 were set to Hyperaldosteronism, familial, type III, MIM# 613677
Review for gene: KCNJ5 was set to GREEN
Added comment: Association with hyperaldosteronism: At least 5 unrelated families reported.

Association with Long QT: disputed.
Sources: Expert Review
Mendeliome v0.7725 HSD11B2 Zornitza Stark Marked gene: HSD11B2 as ready
Mendeliome v0.7725 HSD11B2 Zornitza Stark Gene: hsd11b2 has been classified as Green List (High Evidence).
Mendeliome v0.7725 HSD11B2 Zornitza Stark Phenotypes for gene: HSD11B2 were changed from to Apparent mineralocorticoid excess, MIM# 218030; MONDO:0009025
Mendeliome v0.7724 HSD11B2 Zornitza Stark Publications for gene: HSD11B2 were set to
Mendeliome v0.7723 HSD11B2 Zornitza Stark Mode of inheritance for gene: HSD11B2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7722 HSD11B2 Zornitza Stark reviewed gene: HSD11B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 7670488, 9683587, 17314322; Phenotypes: Apparent mineralocorticoid excess, MIM# 218030, MONDO:0009025; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7722 CLCN2 Zornitza Stark Marked gene: CLCN2 as ready
Mendeliome v0.7722 CLCN2 Zornitza Stark Gene: clcn2 has been classified as Green List (High Evidence).
Mendeliome v0.7722 CLCN2 Zornitza Stark Phenotypes for gene: CLCN2 were changed from to Leukoencephalopathy with ataxia, MIM# 615651; Hyperaldosteronism, familial, type II, MIM# 605635
Mendeliome v0.7721 CLCN2 Zornitza Stark Publications for gene: CLCN2 were set to
Mendeliome v0.7720 CLCN2 Zornitza Stark Mode of inheritance for gene: CLCN2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7719 CLCN2 Zornitza Stark reviewed gene: CLCN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29403011, 29403012, 23707145; Phenotypes: Leukoencephalopathy with ataxia, MIM# 615651, Hyperaldosteronism, familial, type II, MIM# 605635; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7719 CACNA1D Zornitza Stark Marked gene: CACNA1D as ready
Mendeliome v0.7719 CACNA1D Zornitza Stark Gene: cacna1d has been classified as Green List (High Evidence).
Mendeliome v0.7719 CACNA1D Zornitza Stark Phenotypes for gene: CACNA1D were changed from to Primary aldosteronism, seizures, and neurologic abnormalities, MIM# 615474; MONDO:0014200; Sinoatrial node dysfunction and deafness, MIM# 614896
Mendeliome v0.7718 CACNA1D Zornitza Stark Publications for gene: CACNA1D were set to
Mendeliome v0.7717 CACNA1D Zornitza Stark Mode of inheritance for gene: CACNA1D was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7716 CACNA1D Zornitza Stark reviewed gene: CACNA1D: Rating: GREEN; Mode of pathogenicity: None; Publications: 23913001, 32336187, 30698561, 21131953, 15357422, 22678062; Phenotypes: Primary aldosteronism, seizures, and neurologic abnormalities, MIM# 615474, MONDO:0014200, Sinoatrial node dysfunction and deafness, MIM# 614896; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7716 CACNA1H Zornitza Stark Marked gene: CACNA1H as ready
Mendeliome v0.7716 CACNA1H Zornitza Stark Gene: cacna1h has been classified as Green List (High Evidence).
Mendeliome v0.7716 CACNA1H Zornitza Stark Phenotypes for gene: CACNA1H were changed from to Hyperaldosteronism, familial, type IV MIM#617027; MONDO:0014875
Mendeliome v0.7715 CACNA1H Zornitza Stark Publications for gene: CACNA1H were set to
Mendeliome v0.7714 CACNA1H Zornitza Stark Mode of inheritance for gene: CACNA1H was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7713 CACNA1H Zornitza Stark reviewed gene: CACNA1H: Rating: GREEN; Mode of pathogenicity: None; Publications: 27729216, 25907736, 31126930; Phenotypes: Hyperaldosteronism, familial, type IV MIM#617027, MONDO:0014875; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7713 COX16 Zornitza Stark Phenotypes for gene: COX16 were changed from Hypertrophic cardiomyopathy; encephalopathy; severe fatal lactic acidosis to Mitochondrial complex IV deficiency, nuclear type 22, MIM# 619355; Hypertrophic cardiomyopathy; encephalopathy; severe fatal lactic acidosis
Mendeliome v0.7712 COX16 Zornitza Stark reviewed gene: COX16: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 22, MIM# 619355; Mode of inheritance: None
Mendeliome v0.7712 NSF Zornitza Stark Phenotypes for gene: NSF were changed from Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability to Developmental and epileptic encephalopathy 96, MIM# 619340; Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability
Mendeliome v0.7711 NSF Zornitza Stark edited their review of gene: NSF: Changed phenotypes: Developmental and epileptic encephalopathy 96, MIM# 619340, Seizures, EEG with burst suppression, Global developmental delay, Intellectual disability
Mendeliome v0.7711 IPO8 Zornitza Stark Publications for gene: IPO8 were set to
Mendeliome v0.7710 IPO8 Zornitza Stark Classified gene: IPO8 as Green List (high evidence)
Mendeliome v0.7710 IPO8 Zornitza Stark Gene: ipo8 has been classified as Green List (High Evidence).
Mendeliome v0.7709 IPO8 Zornitza Stark edited their review of gene: IPO8: Changed rating: GREEN; Changed publications: 34010604
Mendeliome v0.7709 NFU1 Zornitza Stark Marked gene: NFU1 as ready
Mendeliome v0.7709 NFU1 Zornitza Stark Gene: nfu1 has been classified as Green List (High Evidence).
Mendeliome v0.7709 NFU1 Zornitza Stark Phenotypes for gene: NFU1 were changed from to Multiple mitochondrial dysfunctions syndrome 1, MIM# 605711
Mendeliome v0.7708 NFU1 Zornitza Stark Publications for gene: NFU1 were set to
Mendeliome v0.7707 NFU1 Zornitza Stark Mode of inheritance for gene: NFU1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7706 NFU1 Zornitza Stark reviewed gene: NFU1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21944046, 22077971, 32747156, 29441221; Phenotypes: Multiple mitochondrial dysfunctions syndrome 1, MIM# 605711; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7706 RAB11B Zornitza Stark commented on gene: RAB11B: NDAGSCW is a neurodevelopmental disorder characterized by severely delayed psychomotor development apparent from infancy. Affected individuals have delayed and difficulty walking, intellectual disability, absent speech, and variable additional features, including hip dysplasia, tapering fingers, and seizures. Brain imaging shows decreased cortical white matter, often with decreased cerebellar white matter, thin corpus callosum, and thin brainstem.
Mendeliome v0.7706 RAB11B Zornitza Stark Marked gene: RAB11B as ready
Mendeliome v0.7706 RAB11B Zornitza Stark Gene: rab11b has been classified as Green List (High Evidence).
Mendeliome v0.7706 RAB11B Zornitza Stark Phenotypes for gene: RAB11B were changed from to Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter 617807
Mendeliome v0.7705 RAB11B Zornitza Stark Publications for gene: RAB11B were set to
Mendeliome v0.7704 RAB11B Zornitza Stark Mode of inheritance for gene: RAB11B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7703 RAB11B Zornitza Stark reviewed gene: RAB11B: Rating: GREEN; Mode of pathogenicity: None; Publications: 29106825; Phenotypes: Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter 617807; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7703 UFSP2 Zornitza Stark Marked gene: UFSP2 as ready
Mendeliome v0.7703 UFSP2 Zornitza Stark Gene: ufsp2 has been classified as Green List (High Evidence).
Mendeliome v0.7703 UFSP2 Zornitza Stark Phenotypes for gene: UFSP2 were changed from to Neurodevelopmental disorder; Hip dysplasia, Beukes type, MIM#142669; Spondyloepimetaphyseal dysplasia, Di Rocco type, MIM# 617974
Mendeliome v0.7702 UFSP2 Zornitza Stark Publications for gene: UFSP2 were set to
Mendeliome v0.7701 UFSP2 Zornitza Stark Mode of inheritance for gene: UFSP2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7700 UFSP2 Zornitza Stark changed review comment from: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)]. Likely founder variant in all.

Hip dysplasia: single 8 generation family reported.

Spondyloepimetaphyseal dysplasia, Di Rocco type: two families reported.; to: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)]. Likely founder variant in all. Additional cases identified through the 100,000 Genomes project.

Hip dysplasia: single 8 generation family reported.

Spondyloepimetaphyseal dysplasia, Di Rocco type: two families reported.
Mendeliome v0.7700 UFSP2 Zornitza Stark edited their review of gene: UFSP2: Changed rating: GREEN
Mendeliome v0.7700 KLHL13 Zornitza Stark Marked gene: KLHL13 as ready
Mendeliome v0.7700 KLHL13 Zornitza Stark Gene: klhl13 has been classified as Red List (Low Evidence).
Mendeliome v0.7700 KLHL13 Zornitza Stark gene: KLHL13 was added
gene: KLHL13 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KLHL13 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: KLHL13 were set to 24627108
Phenotypes for gene: KLHL13 were set to HMSN
Review for gene: KLHL13 was set to RED
Added comment: Single family (two affected males) with an inherited peripheral neuropathy, no functional analysis.
Sources: Expert Review
Mendeliome v0.7699 PRX Zornitza Stark Marked gene: PRX as ready
Mendeliome v0.7699 PRX Zornitza Stark Gene: prx has been classified as Green List (High Evidence).
Mendeliome v0.7699 PRX Zornitza Stark Phenotypes for gene: PRX were changed from to Charcot-Marie-Tooth disease, type 4F, MIM# 614895; Dejerine-Sottas disease, MIM# 145900
Mendeliome v0.7698 PRX Zornitza Stark Publications for gene: PRX were set to
Mendeliome v0.7697 PRX Zornitza Stark Mode of inheritance for gene: PRX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7696 PRX Zornitza Stark reviewed gene: PRX: Rating: GREEN; Mode of pathogenicity: None; Publications: 11133365, 11157804, 15197604, 21079185, 22847150, 10839370, 32460404, 31523542, 31426691; Phenotypes: Charcot-Marie-Tooth disease, type 4F, MIM# 614895, Dejerine-Sottas disease, MIM# 145900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7696 PLEKHG5 Zornitza Stark Marked gene: PLEKHG5 as ready
Mendeliome v0.7696 PLEKHG5 Zornitza Stark Gene: plekhg5 has been classified as Green List (High Evidence).
Mendeliome v0.7696 PLEKHG5 Zornitza Stark Phenotypes for gene: PLEKHG5 were changed from to Charcot-Marie-Tooth disease, recessive intermediate C, MIM# 615376; Spinal muscular atrophy, distal, autosomal recessive, 4, MIM# 611067
Mendeliome v0.7695 PLEKHG5 Zornitza Stark Publications for gene: PLEKHG5 were set to
Mendeliome v0.7694 PLEKHG5 Zornitza Stark Mode of inheritance for gene: PLEKHG5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7693 PLEKHG5 Zornitza Stark reviewed gene: PLEKHG5: Rating: GREEN; Mode of pathogenicity: None; Publications: 17564964, 23777631, 23844677, 33492783, 33275839, 33220101, 23777631; Phenotypes: Charcot-Marie-Tooth disease, recessive intermediate C, MIM# 615376, Spinal muscular atrophy, distal, autosomal recessive, 4, MIM# 611067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7693 NEFL Zornitza Stark Marked gene: NEFL as ready
Mendeliome v0.7693 NEFL Zornitza Stark Gene: nefl has been classified as Green List (High Evidence).
Mendeliome v0.7693 NEFL Zornitza Stark Phenotypes for gene: NEFL were changed from to Charcot-Marie-Tooth disease, dominant intermediate G, MIM# 617882; Charcot-Marie-Tooth disease, type 1F, MIM# 607734; Charcot-Marie-Tooth disease, type 2E 607684
Mendeliome v0.7692 NEFL Zornitza Stark Publications for gene: NEFL were set to
Mendeliome v0.7691 NEFL Zornitza Stark Mode of inheritance for gene: NEFL was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7690 NEFL Zornitza Stark reviewed gene: NEFL: Rating: GREEN; Mode of pathogenicity: None; Publications: 10841809, 12393795, 14733962, 24887401, 25877835, 20039262, 12566280, 29191368, 28902413; Phenotypes: Charcot-Marie-Tooth disease, dominant intermediate G, MIM# 617882, Charcot-Marie-Tooth disease, type 1F, MIM# 607734, Charcot-Marie-Tooth disease, type 2E 607684; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7690 ADNP Zornitza Stark Marked gene: ADNP as ready
Mendeliome v0.7690 ADNP Zornitza Stark Gene: adnp has been classified as Green List (High Evidence).
Mendeliome v0.7690 ADNP Zornitza Stark Phenotypes for gene: ADNP were changed from to Helsmoortel-van der Aa syndrome MIM#615873; MONDO:0014379
Mendeliome v0.7689 ADNP Zornitza Stark Publications for gene: ADNP were set to
Mendeliome v0.7688 ADNP Zornitza Stark Mode of inheritance for gene: ADNP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7687 ADNP Zornitza Stark reviewed gene: ADNP: Rating: GREEN; Mode of pathogenicity: None; Publications: 24531329, 25057125, 25533962, 29724491; Phenotypes: Helsmoortel-van der Aa syndrome MIM#615873, MONDO:0014379; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7687 ADNP Elena Savva reviewed gene: ADNP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29911927; Phenotypes: Helsmoortel-van der Aa syndrome MIM#615873; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.7687 CHUK Zornitza Stark Marked gene: CHUK as ready
Mendeliome v0.7687 CHUK Zornitza Stark Gene: chuk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7687 CHUK Zornitza Stark Phenotypes for gene: CHUK were changed from to Popliteal pterygium syndrome, Bartsocas-Papas type 2, MIM# 619339; Cocoon syndrome, MIM# 613630; AEC-like syndrome
Mendeliome v0.7686 CHUK Zornitza Stark Publications for gene: CHUK were set to
Mendeliome v0.7685 CHUK Zornitza Stark Mode of inheritance for gene: CHUK was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7684 CHUK Zornitza Stark Classified gene: CHUK as Amber List (moderate evidence)
Mendeliome v0.7684 CHUK Zornitza Stark Gene: chuk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7683 CHUK Zornitza Stark reviewed gene: CHUK: Rating: AMBER; Mode of pathogenicity: None; Publications: 25691407, 20961246, 10195895, 10195896, 29523099, 28513979; Phenotypes: Popliteal pterygium syndrome, Bartsocas-Papas type 2, MIM# 619339, Cocoon syndrome, MIM# 613630, AEC-like syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7683 TMEM251 Zornitza Stark Phenotypes for gene: TMEM251 were changed from Dysostosis multiplex‐like skeletal dysplasia; severe short stature to Dysostosis multiplex, Ain-Naz type 619345
Mendeliome v0.7682 TMEM251 Zornitza Stark reviewed gene: TMEM251: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Dysostosis multiplex, Ain-Naz type 619345; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7682 PARP6 Zornitza Stark Mode of inheritance for gene: PARP6 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7681 PARP6 Zornitza Stark edited their review of gene: PARP6: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7681 PARP6 Zornitza Stark Marked gene: PARP6 as ready
Mendeliome v0.7681 PARP6 Zornitza Stark Gene: parp6 has been classified as Green List (High Evidence).
Mendeliome v0.7681 PARP6 Zornitza Stark Classified gene: PARP6 as Green List (high evidence)
Mendeliome v0.7681 PARP6 Zornitza Stark Gene: parp6 has been classified as Green List (High Evidence).
Mendeliome v0.7680 PARP6 Zornitza Stark gene: PARP6 was added
gene: PARP6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PARP6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PARP6 were set to Cells 2021, 10(6), 1289; https://doi.org/10.3390/cells10061289
Phenotypes for gene: PARP6 were set to Intellectual disability; Epilepsy; Microcephaly
Review for gene: PARP6 was set to GREEN
Added comment: Four unrelated individuals reported with de novo variants in this gene and a neurodevelopmental phenotype. Supportive functional data. One pair of siblings with a homozygous missense: limited evidence for bi-allelic variants causing disease.
Sources: Literature
Mendeliome v0.7679 MAPKBP1 Zornitza Stark Marked gene: MAPKBP1 as ready
Mendeliome v0.7679 MAPKBP1 Zornitza Stark Gene: mapkbp1 has been classified as Green List (High Evidence).
Mendeliome v0.7679 MAPKBP1 Zornitza Stark Phenotypes for gene: MAPKBP1 were changed from to Nephronophthisis 20, MIM# 617271; MONDO:0014997
Mendeliome v0.7678 MAPKBP1 Zornitza Stark Publications for gene: MAPKBP1 were set to
Mendeliome v0.7677 MAPKBP1 Zornitza Stark Mode of inheritance for gene: MAPKBP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7676 MAPKBP1 Zornitza Stark reviewed gene: MAPKBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28089251, 33623699, 32505465, 32055034; Phenotypes: Nephronophthisis 20, MIM# 617271, MONDO:0014997; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7676 SLC6A6 Zornitza Stark Phenotypes for gene: SLC6A6 were changed from Early retinal degeneration; cardiomyopathy to Hypotaurinaemic retinal degeneration and cardiomyopathy (HTRDC), MIM#145350; Early retinal degeneration; cardiomyopathy
Mendeliome v0.7675 DNAJB2 Zornitza Stark Marked gene: DNAJB2 as ready
Mendeliome v0.7675 DNAJB2 Zornitza Stark Gene: dnajb2 has been classified as Green List (High Evidence).
Mendeliome v0.7675 DNAJB2 Zornitza Stark Phenotypes for gene: DNAJB2 were changed from to Spinal muscular atrophy, distal, autosomal recessive, 5, MIM# 614881; MONDO:0014866
Mendeliome v0.7674 DNAJB2 Zornitza Stark Publications for gene: DNAJB2 were set to
Mendeliome v0.7673 DNAJB2 Zornitza Stark Mode of inheritance for gene: DNAJB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7672 DNAJB2 Zornitza Stark reviewed gene: DNAJB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22522442, 25274842, 33369814, 22522442; Phenotypes: Spinal muscular atrophy, distal, autosomal recessive, 5, MIM# 614881, MONDO:0014866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7672 ATP7A Zornitza Stark Phenotypes for gene: ATP7A were changed from Occipital horn syndrome, 304150; X-linked recessive Menkes disease, 309400 Spinal muscular atrophy, distal, X-linked 3, 300489 to Menkes disease MIM#309400; Occipital horn syndrome MIM#304150; Spinal muscular atrophy, distal, X-linked 3, MIM# 300489
Mendeliome v0.7671 ATP7A Zornitza Stark Publications for gene: ATP7A were set to 21221114
Mendeliome v0.7670 ATP7A Zornitza Stark reviewed gene: ATP7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 20170900, 33137485, 31969342, 31558336; Phenotypes: Menkes disease MIM#309400, Occipital horn syndrome MIM#304150, Spinal muscular atrophy, distal, X-linked 3, MIM# 300489; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females