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Mendeliome v0.4002 AASS Zornitza Stark edited their review of gene: AASS: Changed rating: AMBER
Mendeliome v0.4002 AARS2 Zornitza Stark Phenotypes for gene: AARS2 were changed from to Combined oxidative phosphorylation deficiency 8 MIM#614096; Leukoencephalopathy, progressive, with ovarian failure MIM#615889; MONDO:0013570
Mendeliome v0.3999 AARS2 Zornitza Stark edited their review of gene: AARS2: Changed phenotypes: Combined oxidative phosphorylation deficiency 8 MIM#614096, Leukoencephalopathy, progressive, with ovarian failure MIM#615889, MONDO:0013570
Mendeliome v0.3999 AARS2 Zornitza Stark reviewed gene: AARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30706699, 27839525, 21549344, 25058219, 24808023; Phenotypes: Combined oxidative phosphorylation deficiency 8 MIM#614096, Leukoencephalopathy, progressive, with ovarian failure MIM#615889; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3988 LAMB1 Zornitza Stark Marked gene: LAMB1 as ready
Mendeliome v0.3988 LAMB1 Zornitza Stark Gene: lamb1 has been classified as Green List (High Evidence).
Mendeliome v0.3988 LAMB1 Zornitza Stark Phenotypes for gene: LAMB1 were changed from to Lissencephaly 5, MIM# 615191; Cystic leukoencephalopathy
Mendeliome v0.3987 LAMB1 Zornitza Stark Publications for gene: LAMB1 were set to
Mendeliome v0.3986 LAMB1 Zornitza Stark Mode of inheritance for gene: LAMB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3985 LAMB1 Zornitza Stark reviewed gene: LAMB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23472759, 25925986, 29888467, 25925986, 32548278; Phenotypes: Lissencephaly 5, MIM# 615191, Cystic leukoencephalopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3976 ISPD Zornitza Stark Phenotypes for gene: ISPD were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, MIM# 614643; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7, MIM# 616052
Mendeliome v0.3973 ISPD Zornitza Stark reviewed gene: ISPD: Rating: GREEN; Mode of pathogenicity: None; Publications: 22522421, 23217329, 23390185, 30060766, 28688748, 26404900; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, MIM# 614643, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7, MIM# 616052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3969 MRPL44 Zornitza Stark Phenotypes for gene: MRPL44 were changed from to Combined oxidative phosphorylation deficiency 16, MIM# 615395
Mendeliome v0.3966 MRPL44 Zornitza Stark reviewed gene: MRPL44: Rating: GREEN; Mode of pathogenicity: None; Publications: 23315540, 25797485; Phenotypes: Combined oxidative phosphorylation deficiency 16, MIM# 615395; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3966 KBTBD13 Zornitza Stark Phenotypes for gene: KBTBD13 were changed from to Nemaline myopathy 6, autosomal dominant, MIM# 609273; Hereditary motor neuropathy; late-onset limb girdle muscular dystrophy
Mendeliome v0.3963 KBTBD13 Zornitza Stark reviewed gene: KBTBD13: Rating: ; Mode of pathogenicity: None; Publications: 11731279, 21104864; Phenotypes: Nemaline myopathy 6, autosomal dominant, MIM# 609273, Hereditary motor neuropathy, late-onset limb girdle muscular dystrophy; Mode of inheritance: None
Mendeliome v0.3962 NDUFA13 Zornitza Stark Classified gene: NDUFA13 as Amber List (moderate evidence)
Mendeliome v0.3962 NDUFA13 Zornitza Stark Gene: ndufa13 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3961 NDUFA13 Zornitza Stark edited their review of gene: NDUFA13: Added comment: Second family reported with some supportive functional data.; Changed rating: AMBER; Changed publications: 25901006, 32722639
Mendeliome v0.3961 KBTBD13 Elena Savva reviewed gene: KBTBD13: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 28403181, 31167812, 31671076, 30208948; Phenotypes: Nemaline myopathy 6, autosomal dominant, 609273, Hereditary motor neuropathy, late-onset limb girdle muscular dystrophy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3961 LAMA2 Zornitza Stark Phenotypes for gene: LAMA2 were changed from to Muscular dystrophy, congenital, merosin deficient or partially deficient, MIM# 607855; Muscular dystrophy, limb-girdle, autosomal recessive 23, MIM# 618138
Mendeliome v0.3958 LAMA2 Zornitza Stark reviewed gene: LAMA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30055037; Phenotypes: Muscular dystrophy, congenital, merosin deficient or partially deficient, MIM# 607855, Muscular dystrophy, limb-girdle, autosomal recessive 23, MIM# 618138; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3873 LMBRD2 Zornitza Stark Marked gene: LMBRD2 as ready
Mendeliome v0.3873 LMBRD2 Zornitza Stark Gene: lmbrd2 has been classified as Green List (High Evidence).
Mendeliome v0.3873 LMBRD2 Zornitza Stark Classified gene: LMBRD2 as Green List (high evidence)
Mendeliome v0.3873 LMBRD2 Zornitza Stark Gene: lmbrd2 has been classified as Green List (High Evidence).
Mendeliome v0.3872 LMBRD2 Zornitza Stark gene: LMBRD2 was added
gene: LMBRD2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LMBRD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LMBRD2 were set to 32820033; https://doi.org/10.1101/797787
Phenotypes for gene: LMBRD2 were set to Global developmental delay; Intellectual disability; Microcephaly; Seizures; Abnormality of nervous system morphology; Abnormality of the eye
Mode of pathogenicity for gene: LMBRD2 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: LMBRD2 was set to GREEN
Added comment: 13 individuals with dn missense SNVs overall, overlapping features for 10 with available phenotype / a recurring variant has been identified in 2 different studies.

► Malhotra et al (2020 - PMID: 32820033) report on 10 unrelated individuals with de novo missense LMBRD2 variants. Features included DD (9/10), ID (6/8 of relevant age), microcephaly (7/10), seizures (5/10 - >=3 different variants), structural brain abnormalities (e.g. thin CC in 6/9), highly variable ocular abnormalities (5/10) and dysmorphic features in some (7/10 - nonspecific). All had variable prior non-diagnostic genetic tests (CMA, gene panel, mendeliome, karyotype). WES/WGS revealed LMBRD2 missense variants, in all cases de novo. A single individual had additional variants with weaker evidence of pathogenicity. 5 unique missense SNVs and 2 recurrent ones (NM_001007527:c.367T>C - p.Trp123Arg / c.1448G>A - p.Arg483His) were identified. These occurred in different exons. Variants were not present in gnomAD and all had several in silico predictions in favor of a deleterious effect. There was phenotypic variability among individuals with the same variant (e.g. seizures in 1/3 and microchephaly in 2/3 of those harboring R483H). The gene has a pLI of 0 (although o/e ranges from 0.23 to 0.55), %HI of 15.13 and z-score of 2.27. The authors presume that haploinsufficiency may not apply, and consider a gain-of-function/dominant-negative effect more likely. As the authors comment LMBRD2 (LMBR1 domain containing 2) encodes a membrane bound protein with poorly described function. It is widely expressed across tissues with notable expression in human brain (also in Drosophila, or Xenopus laevis). It displays high interspecies conservation. It has been suggested (Paek et al - PMID: 28388415) that LMBRD2 is a potential regulator of β2 adrenoreceptor signalling through involvement in GPCR signalling.

► Kaplanis et al (2020 - https://doi.org/10.1101/797787) in a dataset of 31058 parent-offspring trios (WES) previously identified 3 individuals with developmental disorder, harboring c.1448G>A - p.Arg483His. These individuals (1 from the DDD study, and 2 GeneDx patients) appear in Decipher. [ https://decipher.sanger.ac.uk/ddd/research-variant/40e17c78cc9655a6721006fc1e0c98db/overview ]. The preprint by Kaplanis et al is cited by Malhotra et al, with Arg483His reported in 6 patients overall in both studies.
Sources: Literature
Mendeliome v0.3847 HNRNPA2B1 Zornitza Stark Gene: hnrnpa2b1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3847 HNRNPA2B1 Zornitza Stark Classified gene: HNRNPA2B1 as Amber List (moderate evidence)
Mendeliome v0.3847 HNRNPA2B1 Zornitza Stark Gene: hnrnpa2b1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3846 HNRNPA2B1 Zornitza Stark gene: HNRNPA2B1 was added
gene: HNRNPA2B1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HNRNPA2B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPA2B1 were set to 23455423; 30279180; 29358076; 26744327; 23635965
Phenotypes for gene: HNRNPA2B1 were set to Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 MIM#615422
Review for gene: HNRNPA2B1 was set to AMBER
Added comment: One family reported that segregates cognitive impairment as part of the phenotype, and extensive functional analysis of protein, including a drosophila model.
Sources: Literature
Mendeliome v0.3845 PSMC3 Zornitza Stark Gene: psmc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3845 PSMC3 Zornitza Stark Classified gene: PSMC3 as Amber List (moderate evidence)
Mendeliome v0.3845 PSMC3 Zornitza Stark Gene: psmc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3844 PSMC3 Zornitza Stark gene: PSMC3 was added
gene: PSMC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMC3 were set to 32500975
Phenotypes for gene: PSMC3 were set to Deafness; cataract
Review for gene: PSMC3 was set to AMBER
Added comment: Three affected individuals from a single consanguineous family reported with homozygous intronic variant. Animal model.
Sources: Literature
Mendeliome v0.3835 TAF1C Zornitza Stark Gene: taf1c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3835 TAF1C Zornitza Stark Classified gene: TAF1C as Amber List (moderate evidence)
Mendeliome v0.3835 TAF1C Zornitza Stark Gene: taf1c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3834 TAF1C Zornitza Stark gene: TAF1C was added
gene: TAF1C was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TAF1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAF1C were set to 32779182
Phenotypes for gene: TAF1C were set to Global developmental delay; Intellectual disability; Spasticity; Strabismus; Seizures; Abnormality of nervous system morphology
Review for gene: TAF1C was set to AMBER
Added comment: Knuutinen et al (2020 - PMID: 32779182) report on 2 individuals from 2 consanguineous families, homozygous for TAF1C missense variants. Both presented with an early onset neurological phenotype with severe global DD, ID (2/2 - moderate and profound), spasticity (2/2), ophthalmic findings (strabismus 2/2, nystagmus 1/2). Epilepsy, abnormal brain MRI (cerebral and cerebellar atrophy and white matter hyperintensities) as well and additional findings were reported in one (always the same individual). Following a normal CMA, exome in the first case revealed a homozygous missense SNV (NM_005679.3:c.1165C>T / p.Arg389Cys) supported by in silico predictions. mRNA and protein levels were substantially reduced in fibroblasts from this subject. Only the patient and parents were tested for the variant but not 3 unaffected sibs (fig1). The second individual was homozygous for another missense variant (p.Arg405Cys) also supported by in silico predictions. The girl was the single affected person within the family with an unaffected sib and parents heterozygous for the variant. Several other unaffected relatives in the extended pedigree were either carriers for this variant or homozygous for the wt allele. TAF1C encodes the TATA-box binding protein associated factor (TAF) RNA polymerase I subunit. RNA polymerase I (Pol I) transcribes genes to produce rRNA. For Pol I to initiate transcription, two transcription factors are required : UBF (upstream binding factor encoded by UBTF) and SL1 (selectivity factor 1). The latter is formed by TBP (TATA-binding protein) and 3 Pol I-specific TBP-associated factors (TAFs). A recurrent de novo missense variant in UBTF (encoding the other Pol I transcription factor) causes a disorder with highly similar features. The specific variant acts through a gain-of-function mechanism (and not by LoF which appears to apply for TAF1C based on expression data). The authors hypothesize that altered Pol I activity and resulting ribosomal stress could cause the microcephaly and leukodystrophy (both reported in 1 - the same - individual).
Sources: Expert list
Mendeliome v0.3806 VKORC1 Zornitza Stark reviewed gene: VKORC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14765194, 21900891, 28198005; Phenotypes: Vitamin K-dependent clotting factors, combined deficiency of, 2, MIM# 607473, Warfarin resistance, MIM# 122700; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3805 TPM4 Zornitza Stark gene: TPM4 was added
gene: TPM4 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TPM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TPM4 were set to 28134622; 31249973; 21153663
Phenotypes for gene: TPM4 were set to Macrothrombocytopaenia
Review for gene: TPM4 was set to GREEN
Added comment: Three families reported in addition to genome-wide association studies in nearly 70,000 individuals which indicate that SNVs in TPM4 exert an effect on the count and volume of platelets.
Sources: Expert list
Mendeliome v0.3804 THPO Zornitza Stark Phenotypes for gene: THPO were changed from to Thrombocythemia 1, MIM# 187950
Mendeliome v0.3801 THPO Zornitza Stark reviewed gene: THPO: Rating: GREEN; Mode of pathogenicity: None; Publications: 9425899, 10583217; Phenotypes: Thrombocythemia 1, MIM# 187950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3799 THBD Zornitza Stark edited their review of gene: THBD: Added comment: Variants in this gene have also been linked to thrombophilia. Two families reported with a bleeding disorder, both variants located in the transmembrane domain.; Changed publications: 29500241, 19625716, 25564403, 32634856; Changed phenotypes: {Hemolytic uremic syndrome, atypical, susceptibility to, 6}, MIM# 612926, Bleeding disorder
Mendeliome v0.3796 SRC Zornitza Stark gene: SRC was added
gene: SRC was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SRC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRC were set to 31204551; 26936507
Phenotypes for gene: SRC were set to Thrombocytopaenia 6, MIM# 616937
Review for gene: SRC was set to GREEN
Added comment: Two families, and convincing functional data including animal model.
Sources: Expert list
Mendeliome v0.3793 PTPRJ Zornitza Stark Gene: ptprj has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3793 PTPRJ Zornitza Stark Classified gene: PTPRJ as Amber List (moderate evidence)
Mendeliome v0.3793 PTPRJ Zornitza Stark Gene: ptprj has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3792 PTPRJ Zornitza Stark gene: PTPRJ was added
gene: PTPRJ was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PTPRJ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPRJ were set to 30591527
Phenotypes for gene: PTPRJ were set to Thrombocytopaenia
Review for gene: PTPRJ was set to AMBER
Added comment: Two siblings reported with nonsyndromic thrombocytopenia characterised by spontaneous bleeding, small-sized platelets, and impaired platelet responses to the GPVI agonists collagen and convulxin. Supportive zebrafish model.
Sources: Expert list
Mendeliome v0.3791 PTGS1 Zornitza Stark Gene: ptgs1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3791 PTGS1 Zornitza Stark Classified gene: PTGS1 as Amber List (moderate evidence)
Mendeliome v0.3791 PTGS1 Zornitza Stark Gene: ptgs1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3790 PTGS1 Zornitza Stark gene: PTGS1 was added
gene: PTGS1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PTGS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTGS1 were set to 32299908; 11442478; 27629384; 8562397
Phenotypes for gene: PTGS1 were set to Platelet dysfunction; bleeding
Review for gene: PTGS1 was set to AMBER
Added comment: Single molecularly characterised family reported. However, note at least two previous older reports where deficiency was identified at protein rather than gene level.
Sources: Expert list
Mendeliome v0.3783 MPIG6B Zornitza Stark gene: MPIG6B was added
gene: MPIG6B was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MPIG6B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPIG6B were set to 31276734; 29898956; 27743390
Phenotypes for gene: MPIG6B were set to Thrombocytopenia, anemia, and myelofibrosis, MIM# 617441
Review for gene: MPIG6B was set to GREEN
Added comment: Six families reported.
Sources: Expert list
Mendeliome v0.3782 MAT2A Zornitza Stark Gene: mat2a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3779 MAT2A Zornitza Stark Classified gene: MAT2A as Amber List (moderate evidence)
Mendeliome v0.3779 MAT2A Zornitza Stark Gene: mat2a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3778 MAT2A Zornitza Stark reviewed gene: MAT2A: Rating: AMBER; Mode of pathogenicity: None; Publications: 30071989, 25557781; Phenotypes: Thoracic aortic aneurysm; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3775 KDSR Zornitza Stark Phenotypes for gene: KDSR were changed from to Erythrokeratodermia variabilis et progressiva 4, MIM# 617526; severe thrombocytopaenia
Mendeliome v0.3772 KDSR Zornitza Stark reviewed gene: KDSR: Rating: GREEN; Mode of pathogenicity: None; Publications: 28774589, 30467204, 28575652; Phenotypes: Erythrokeratodermia variabilis et progressiva 4, MIM# 617526, severe thrombocytopaenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3772 GGCX Zornitza Stark Phenotypes for gene: GGCX were changed from to Vitamin K-dependent clotting factors, combined deficiency of, 1, MIM# 277450
Mendeliome v0.3769 GGCX Zornitza Stark reviewed gene: GGCX: Rating: GREEN; Mode of pathogenicity: None; Publications: 32785662, 30531603, 26758921; Phenotypes: Vitamin K-dependent clotting factors, combined deficiency of, 1, MIM# 277450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3752 EPHB2 Zornitza Stark Gene: ephb2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3749 EPHB2 Zornitza Stark Classified gene: EPHB2 as Amber List (moderate evidence)
Mendeliome v0.3749 EPHB2 Zornitza Stark Gene: ephb2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3748 EPHB2 Zornitza Stark reviewed gene: EPHB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30213874, 25370417; Phenotypes: Bleeding disorder, platelet-type, 22, MIM# 618462; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3743 CSTB Ain Roesley reviewed gene: CSTB: Rating: AMBER; Mode of pathogenicity: None; Publications: 28457472; Phenotypes: Keratolytic winter erythema (MIM#148370); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3715 B3GNT2 Zornitza Stark Classified gene: B3GNT2 as Amber List (moderate evidence)
Mendeliome v0.3715 B3GNT2 Zornitza Stark Gene: b3gnt2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3714 B3GNT2 Zornitza Stark edited their review of gene: B3GNT2: Added comment: Gene previously known as B3GNT1. Two families reported.; Changed rating: AMBER; Changed publications: 23359570, 23877401; Changed phenotypes: Muscular dystrophy-dystroglycanopathy; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3707 HYLS1 Zornitza Stark Added comment: Comment when marking as ready: Borderline Amber/Green and mechanism unclear. However, given at least two variants reported with a ciliopathy phenotype and supporting functional data from multiple animal models all indicative of ciliopathy, keep Green.
Mendeliome v0.3703 HYLS1 Melanie Marty reviewed gene: HYLS1: Rating: AMBER; Mode of pathogenicity: Other; Publications: 15843405, 18648327, 19400947, 19656802, 32509774; Phenotypes: Hydrolethalus syndrome (MIM#236680); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3678 AIFM1 Zornitza Stark Phenotypes for gene: AIFM1 were changed from to Combined oxidative phosphorylation deficiency 6, 300816; Cowchock syndrome, 310490; Deafness, X-linked 5, 300614; Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy, 300232
Mendeliome v0.3675 AIFM1 Elena Savva reviewed gene: AIFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28842795; Phenotypes: Combined oxidative phosphorylation deficiency 6, 300816, Cowchock syndrome, 310490, Deafness, X-linked 5, 300614, Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy, 300232; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3674 SEC61B Zornitza Stark Gene: sec61b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3674 SEC61B Zornitza Stark Classified gene: SEC61B as Amber List (moderate evidence)
Mendeliome v0.3674 SEC61B Zornitza Stark Gene: sec61b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3673 SEC61B Zornitza Stark gene: SEC61B was added
gene: SEC61B was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SEC61B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEC61B were set to 28862642; 30652979; 28375157
Phenotypes for gene: SEC61B were set to Polycystic liver disease with or without renal cysts
Review for gene: SEC61B was set to AMBER
Added comment: Two unrelated individuals reported.
Sources: Expert list
Mendeliome v0.3670 C3orf52 Zornitza Stark Gene: c3orf52 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3670 C3orf52 Zornitza Stark Classified gene: C3orf52 as Amber List (moderate evidence)
Mendeliome v0.3670 C3orf52 Zornitza Stark Gene: c3orf52 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3669 C3orf52 Zornitza Stark gene: C3orf52 was added
gene: C3orf52 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C3orf52 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C3orf52 were set to 32336749
Phenotypes for gene: C3orf52 were set to Localized hypotrichosis
Review for gene: C3orf52 was set to AMBER
Added comment: 2 families with 4 individuals with localised hypotrichosis and homozygous variants in C3ORF52. C3ORF52 was found to be coexpressed with lipase H in the inner root sheath of the hair follicle and the two proteins were found to directly interact. The LAH-causing variants were associated with decreased C3ORF52 expression and resulted in markedly reduced lipase H–mediated 2-acyl-lysophosphatidic acid (LPA) biosynthesis. Same pathway as two other genes for localised hypotrichosis (LIPH and LPAR6)
Sources: Literature
Mendeliome v0.3666 DLG5 Zornitza Stark gene: DLG5 was added
gene: DLG5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLG5 were set to 32631816
Phenotypes for gene: DLG5 were set to Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations
Review for gene: DLG5 was set to GREEN
Added comment: Four unrelated families reported, supportive Xenopus animal model data.
Sources: Literature
Mendeliome v0.3665 AHR Zornitza Stark Gene: ahr has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3665 AHR Zornitza Stark Classified gene: AHR as Amber List (moderate evidence)
Mendeliome v0.3665 AHR Zornitza Stark Gene: ahr has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3657 CALCRL Hazel Phillimore gene: CALCRL was added
gene: CALCRL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CALCRL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CALCRL were set to PMID: 30115739
Phenotypes for gene: CALCRL were set to ?Lymphatic malformation 8 (MIM# 618773); hydrops fetalis
Review for gene: CALCRL was set to RED
Added comment: Homozygous in-frame deletion (Val205del) in the CALCRL gene (Val205del) in a 22 week-old fetus with hydrops details due to lymphatic malformation. Consanguineous parents.
Heterozygosity of the variant was also suggested to be associated with spontaneous miscarriage and subfertility. Consanguineous family with 8 total miscarriages from 3 carrier women, and 2 of these were confirmed to be due to hydrops fetalis.
Note: possible association of a variant in ASAH1 gene that is associated with Farber lipogranulomatosis which can sometimes present with antenatal hydrops fetalis. (Homozygosity in one of the fetuses, fetus and heterozygosity in some of the family members).
In vitro biochemical assays indicated that the variant causes misfolding of the protein and reduced association with its chaperone, RAMP2, and reduced translocation to the plasma membrane. (PMID: 30115739; Mackie, DI. et al., 2018).
Sources: Literature
Mendeliome v0.3657 RELN Chern Lim reviewed gene: RELN: Rating: AMBER; Mode of pathogenicity: None; Publications: 32001840; Phenotypes: ankylosing spondylitis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3657 AHR Chern Lim gene: AHR was added
gene: AHR was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AHR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AHR were set to 29726989; 31896775
Phenotypes for gene: AHR were set to ?Retinitis pigmentosa 85 MIM#618345; foveal hypoplasia and infantile nystagmus
Review for gene: AHR was set to AMBER
Added comment: - One reported homozygous splice variant in a consanguineous family & a mouse model (PMID: 29726989)

- A homozygous nonsense variant in 1 consanguineous family with foveal hypoplasia and infantile nystagmus (PMID:31896775).
Sources: Literature
Mendeliome v0.3649 MYLPF Zornitza Stark Gene: mylpf has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3649 MYLPF Zornitza Stark Classified gene: MYLPF as Amber List (moderate evidence)
Mendeliome v0.3649 MYLPF Zornitza Stark Gene: mylpf has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3647 FBXL7 Hazel Phillimore gene: FBXL7 was added
gene: FBXL7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FBXL7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FBXL7 were set to PMID: 31633297
Phenotypes for gene: FBXL7 were set to Hennekam lymphangiectasia-lymphedema syndrome; lymphedema; protein‐losing enteropathy; dental anomalies; camptodactyly; microtia; small auditory canals; ductive hearing loss; middle ear anomalies, bifid scrotum, and facial dysmorphic features including hypertelorism, telecanthus, epicanthal folds, downslanting palpebral fissures, broad and depressed nasal bridge, and thickened nasal alae.
Review for gene: FBXL7 was set to AMBER
Added comment: Homozygous deletion of exon 3 of FBXL7 (predicted to be in-frame) in a 2-year old with novel form of Hennekam syndrome. Each parent was heterozygous.
Patient had lymphedema, protein‐losing enteropathy, dental anomalies, camptodactyly, microtia, small auditory canals, ductive hearing loss, middle ear anomalies, bifid scrotum, and facial dysmorphic features including hypertelorism, telecanthus, epicanthal folds, downslanting palpebral fissures, broad and depressed nasal bridge, and thickened nasal alae.
Sources: Literature
Mendeliome v0.3647 PJA1 Zornitza Stark Gene: pja1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3647 PJA1 Zornitza Stark Classified gene: PJA1 as Amber List (moderate evidence)
Mendeliome v0.3647 PJA1 Zornitza Stark Gene: pja1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3646 PJA1 Zornitza Stark gene: PJA1 was added
gene: PJA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PJA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PJA1 were set to 32530565
Phenotypes for gene: PJA1 were set to Intellectual disability; trigonocephaly
Review for gene: PJA1 was set to AMBER
Added comment: Recurrent variant, p.Arg376Cys, reported in 7 Japanese individuals, supportive mouse model. Individuals shared a common haplotype, suggestive of founder effect
Sources: Literature
Mendeliome v0.3643 NARS Zornitza Stark gene: NARS was added
gene: NARS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NARS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NARS were set to 32738225
Phenotypes for gene: NARS were set to Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy
Review for gene: NARS was set to GREEN
Added comment: [Please note that HGNC Approved Gene Symbol for this gene is NARS1] Manole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families. Similar features were reported for AR/AD occurrences of the disorder and included microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features. NARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported. Some variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all]. The authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model).
Sources: Literature
Mendeliome v0.3642 ZNF407 Zornitza Stark Gene: znf407 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3639 ZNF407 Zornitza Stark Classified gene: ZNF407 as Amber List (moderate evidence)
Mendeliome v0.3639 ZNF407 Zornitza Stark Gene: znf407 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3638 ZNF407 Zornitza Stark reviewed gene: ZNF407: Rating: AMBER; Mode of pathogenicity: None; Publications: 24907849, 32737394, 23195952; Phenotypes: Global developmental delay, Intellectual disability; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3627 AMBRA1 Bryony Thompson Marked gene: AMBRA1 as ready
Mendeliome v0.3627 AMBRA1 Bryony Thompson Gene: ambra1 has been classified as Green List (High Evidence).
Mendeliome v0.3627 AMBRA1 Bryony Thompson Classified gene: AMBRA1 as Green List (high evidence)
Mendeliome v0.3627 AMBRA1 Bryony Thompson Gene: ambra1 has been classified as Green List (High Evidence).
Mendeliome v0.3626 AMBRA1 Bryony Thompson gene: AMBRA1 was added
gene: AMBRA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AMBRA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AMBRA1 were set to 17589504; 32333458
Phenotypes for gene: AMBRA1 were set to Neural tube defects
Review for gene: AMBRA1 was set to GREEN
Added comment: 5 rare missense variants were identified in 6 cases from a neural tube defect cohort, and 4 (p.Thr80Met, p.Leu274Phe, p.Ser743Phe, and p.Met884Val) of them were functionally validated to affect autophagy regulation in vitro or zebrafish embryo development in vivo. There is also null mouse model with neural tube defects.
Sources: Literature
Mendeliome v0.3622 WDR1 Zornitza Stark Phenotypes for gene: WDR1 were changed from to Periodic fever, immunodeficiency, and thrombocytopenia syndrome, MIM#150550; Neutropaenia; Poor wound healing; Severe stomatitis; Neutrophil nuclei herniate; Autoinflammatory periodic fever; Thrombocytopaenia
Mendeliome v0.3619 WDR1 Zornitza Stark reviewed gene: WDR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27994071, 27557945, 29751004; Phenotypes: Periodic fever, immunodeficiency, and thrombocytopenia syndrome, MIM#150550, Neutropaenia, Poor wound healing, Severe stomatitis, Neutrophil nuclei herniate, Autoinflammatory periodic fever, Thrombocytopaenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3619 KREMEN1 Bryony Thompson Gene: kremen1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3619 KREMEN1 Bryony Thompson Classified gene: KREMEN1 as Amber List (moderate evidence)
Mendeliome v0.3619 KREMEN1 Bryony Thompson Gene: kremen1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3618 KREMEN1 Bryony Thompson gene: KREMEN1 was added
gene: KREMEN1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: KREMEN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KREMEN1 were set to 27049303; 27550540
Phenotypes for gene: KREMEN1 were set to Ectodermal dysplasia 13, hair/tooth type MIM#617392
Review for gene: KREMEN1 was set to AMBER
Added comment: 4 consanguineous Palestinian families segregating the same homozygous missense (Phe209Ser) with disease phenotype which includes hair abnormalities. Possible founder variant. There are also animal model functional assays that suggest the gene is involved in hair development.
Sources: Expert list
Mendeliome v0.3616 ANO1 Zornitza Stark Gene: ano1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3615 ANO1 Zornitza Stark Classified gene: ANO1 as Amber List (moderate evidence)
Mendeliome v0.3615 ANO1 Zornitza Stark Gene: ano1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3608 OTX2 Zornitza Stark Phenotypes for gene: OTX2 were changed from to Microphthalmia, syndromic 5, MIM# 610125; Pituitary hormone deficiency, combined, 6, MIM# 613986; Retinal dystrophy, early-onset, with or without pituitary dysfunction, MIM# 610125
Mendeliome v0.3606 OTX2 Zornitza Stark reviewed gene: OTX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microphthalmia, syndromic 5, MIM# 610125, Pituitary hormone deficiency, combined, 6, MIM# 613986, Retinal dystrophy, early-onset, with or without pituitary dysfunction, MIM# 610125; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3595 GNPNAT1 Zornitza Stark Gene: gnpnat1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3595 GNPNAT1 Zornitza Stark Classified gene: GNPNAT1 as Amber List (moderate evidence)
Mendeliome v0.3595 GNPNAT1 Zornitza Stark Gene: gnpnat1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3590 GNPNAT1 Arina Puzriakova edited their review of gene: GNPNAT1: Changed rating: AMBER
Mendeliome v0.3590 GNPNAT1 Arina Puzriakova changed review comment from: Four affected sibs from a consanguineous Pakistani family with skeletal dysplasia, characterised by severe short stature, rhizomelic shortening of the limbs, and metacarpal and metatarsal length irregularities in the hands and feet. WGS revealed a homozygous missense variant (c.226G>A; p.Glu76Lys) in GNPNAT1, which segregating with the phenotype.
Gnpnat1 gene knockdown in primary rat chondrocytes decreased cellular proliferation and expression of chondrocyte differentiation markers, indicating the importance of Gnpnat1 for growth plate chondrocyte proliferation and differentiation.
Sources: Literature; to: PMID: 32591345 (2020) - Four affected sibs from a consanguineous Pakistani family with skeletal dysplasia, characterised by severe short stature, rhizomelic shortening of the limbs, and metacarpal and metatarsal length irregularities in the hands and feet. WGS revealed a homozygous missense variant (c.226G>A; p.Glu76Lys) in GNPNAT1, which segregating with the phenotype.
Gnpnat1 gene knockdown in primary rat chondrocytes decreased cellular proliferation and expression of chondrocyte differentiation markers, indicating the importance of Gnpnat1 for growth plate chondrocyte proliferation and differentiation. Additional cases required to validate pathogenicity of GNPNAT1.
Sources: Literature
Mendeliome v0.3590 GNPNAT1 Arina Puzriakova gene: GNPNAT1 was added
gene: GNPNAT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GNPNAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNPNAT1 were set to 32591345
Phenotypes for gene: GNPNAT1 were set to Rhizomelic skeletal dysplasia
Review for gene: GNPNAT1 was set to RED
Added comment: Four affected sibs from a consanguineous Pakistani family with skeletal dysplasia, characterised by severe short stature, rhizomelic shortening of the limbs, and metacarpal and metatarsal length irregularities in the hands and feet. WGS revealed a homozygous missense variant (c.226G>A; p.Glu76Lys) in GNPNAT1, which segregating with the phenotype.
Gnpnat1 gene knockdown in primary rat chondrocytes decreased cellular proliferation and expression of chondrocyte differentiation markers, indicating the importance of Gnpnat1 for growth plate chondrocyte proliferation and differentiation.
Sources: Literature
Mendeliome v0.3586 IVNS1ABP Bryony Thompson gene: IVNS1ABP was added
gene: IVNS1ABP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IVNS1ABP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IVNS1ABP were set to 32499645
Phenotypes for gene: IVNS1ABP were set to Primary immunodeficiency
Review for gene: IVNS1ABP was set to GREEN
Added comment: 3 unrelated families with putative loss of function variants. Case features and immunophenotyping of patient cells is suggestive of a combined immune deficiency, based on the ESID definitions of PID subtypes.
Sources: Literature
Mendeliome v0.3585 PTPN2 Bryony Thompson Gene: ptpn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3585 PTPN2 Bryony Thompson Classified gene: PTPN2 as Amber List (moderate evidence)
Mendeliome v0.3585 PTPN2 Bryony Thompson Gene: ptpn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3584 PTPN2 Bryony Thompson gene: PTPN2 was added
gene: PTPN2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTPN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN2 were set to 32499645; 27658548
Phenotypes for gene: PTPN2 were set to Lupus; arthritis; common variable immunodeficiency
Review for gene: PTPN2 was set to AMBER
Added comment: A single family with a proband diagnosed with CVID and arthiritis (among other features) with an intronic expression quantitative trait loci (eQTL) rs2847297-G in trans with a stopgain variant. The stopgain variant was also identified in the proband's mother, who was diagnosed with lupus. A Ptpn2 deficient mouse model also demonstrates an autoimmune phenotype.
Sources: Literature
Mendeliome v0.3581 MRPS23 Zornitza Stark Phenotypes for gene: MRPS23 were changed from Hepatic disease; Combined respiratory chain complex deficienciesHepatic disease; Combined respiratory chain complex deficiencies; Cardiomyopathy; Tubulopathy; Lactic acidosis; Structural brain abnormalities to Hepatic disease; Combined respiratory chain complex deficiencies; Hepatic disease; Combined respiratory chain complex deficiencies; Cardiomyopathy; Tubulopathy; Lactic acidosis; Structural brain abnormalities; Combined oxidative phosphorylation deficiency 45, MIM#618951
Mendeliome v0.3580 MRPS23 Zornitza Stark edited their review of gene: MRPS23: Changed phenotypes: Hepatic disease, Combined respiratory chain complex deficiencies, Cardiomyopathy, Tubulopathy, Lactic acidosis, Structural brain abnormalities, Combined oxidative phosphorylation deficiency 45, MIM#618951
Mendeliome v0.3580 MRPL12 Zornitza Stark Phenotypes for gene: MRPL12 were changed from Growth retardation; neurological deterioration; mitochondrial translation deficiency to Growth retardation; neurological deterioration; mitochondrial translation deficiency; Combined oxidative phosphorylation deficiency 45, MIM#618951
Mendeliome v0.3579 MRPL12 Zornitza Stark edited their review of gene: MRPL12: Changed phenotypes: Growth retardation, neurological deterioration, mitochondrial translation deficiency, Combined oxidative phosphorylation deficiency 45, MIM#618951
Mendeliome v0.3561 TRIM63 Ain Roesley gene: TRIM63 was added
gene: TRIM63 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRIM63 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM63 were set to 30681346; 32451364
Phenotypes for gene: TRIM63 were set to Hypertrophic cardiomyopathy
Penetrance for gene: TRIM63 were set to unknown
Review for gene: TRIM63 was set to GREEN
Added comment: PMID: 30681346;
LIMITED by Clingen working group (last evaluated 2018)

PMID: 32451364
- 16 index cases with rare homozygous or compound heterozygous variants (15 HCM and one restrictive cardiomyopathy). None of these variants have homozygote counts in gnomAD.
- segregated in 3 families
- 1 index had another pathogenic truncating variant in MYBPC3
- 5 missense and 3 PTCs
- Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy
Sources: Literature
Mendeliome v0.3561 KRT71 Bryony Thompson Gene: krt71 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3561 KRT71 Bryony Thompson Classified gene: KRT71 as Amber List (moderate evidence)
Mendeliome v0.3561 KRT71 Bryony Thompson Gene: krt71 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3560 KRT71 Bryony Thompson gene: KRT71 was added
gene: KRT71 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KRT71 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRT71 were set to 14632181; 22592156; 19713490
Phenotypes for gene: KRT71 were set to ?Hypotrichosis 13, 615896
Review for gene: KRT71 was set to AMBER
Added comment: A single family with 3 affected members of a 3-generation Japanese family segregating a missense variant (F141C) with autosomal dominant woolly hair/hypotrichosis, with supporting functional assays and animal models.
Sources: Literature
Mendeliome v0.3539 LARS Zornitza Stark Added comment: Comment when marking as ready: Lenz et al (2020 - PMID: 32699352) review the phenotype of 25 affected individuals from 15 families.

Seizures occurred in 19/24 and were commonly associated with infections. Encephalopathic episodes (in 13 patients) accompanied by seizures up to status epilepticus occurred independently of hepatic decompensation.

In addition 22/24 presented with neurodevelopmental delay. The authors comment that cognitive impairment was present in 13/17 individuals (mild-severe) whereas most presented with learning disabilities.

These patients will most likely investigated for their liver disease (although presentation was highly variable and/or very mild in few).

The gene encodes a cytoplasmic amino-acyl tRNA synthetase (ARS) with neurologic manifestations observed in almost all patients (and seizures / DD and ID common to other disorders due to mutations in other genes encoding for ARSs).

Please note that the HGNC approved symbol for this gene is LARS1.
Mendeliome v0.3536 CTRC Zornitza Stark Gene: ctrc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3533 CTRC Zornitza Stark Classified gene: CTRC as Amber List (moderate evidence)
Mendeliome v0.3533 CTRC Zornitza Stark Gene: ctrc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3532 CTRC Zornitza Stark reviewed gene: CTRC: Rating: AMBER; Mode of pathogenicity: None; Publications: 18059268, 18172691, 28502372; Phenotypes: {Pancreatitis, chronic, susceptibility to}, MIM#167800; Mode of inheritance: Other
Mendeliome v0.3529 CLDN2 Zornitza Stark Gene: cldn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3526 CLDN2 Zornitza Stark Classified gene: CLDN2 as Amber List (moderate evidence)
Mendeliome v0.3526 CLDN2 Zornitza Stark Gene: cldn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3525 CLDN2 Zornitza Stark reviewed gene: CLDN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29884332, 31163246; Phenotypes: Susceptibility to pancreatitis; Mode of inheritance: Other
Mendeliome v0.3525 BMP10 Zornitza Stark Gene: bmp10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3525 BMP10 Zornitza Stark Classified gene: BMP10 as Amber List (moderate evidence)
Mendeliome v0.3525 BMP10 Zornitza Stark Gene: bmp10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3524 BMP10 Zornitza Stark gene: BMP10 was added
gene: BMP10 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: BMP10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP10 were set to 30578383
Phenotypes for gene: BMP10 were set to Pulmonary arterial hypertension
Review for gene: BMP10 was set to AMBER
Added comment: A truncating mutation and a predicted loss-of-function missense variant were identified in BMP10 in two severely affected sporadic PAH female patients.
Sources: Expert list
Mendeliome v0.3523 SMAD1 Zornitza Stark Gene: smad1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3523 SMAD1 Zornitza Stark Classified gene: SMAD1 as Amber List (moderate evidence)
Mendeliome v0.3523 SMAD1 Zornitza Stark Gene: smad1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3522 SMAD1 Zornitza Stark gene: SMAD1 was added
gene: SMAD1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SMAD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD1 were set to 21898662; 23478097
Phenotypes for gene: SMAD1 were set to Pulmonary arterial hypertension
Review for gene: SMAD1 was set to AMBER
Added comment: One missense variant identified in a PAH case. Mouse model is consistent with pulmonary hypertension.
Sources: Expert list
Mendeliome v0.3502 MPL Zornitza Stark Phenotypes for gene: MPL were changed from to Myelofibrosis with myeloid metaplasia, somatic, MIM#2544503; Thrombocythemia 2, MIM#601977, AD, SMu; Thrombocytopenia, congenital amegakaryocytic, MIM#604498, AR
Mendeliome v0.3496 MPL Chern Lim reviewed gene: MPL: Rating: GREEN; Mode of pathogenicity: None; Publications: 28955303, 26423830; Phenotypes: Myelofibrosis with myeloid metaplasia, somatic, MIM#2544503, Thrombocythemia 2, MIM#601977, AD, SMu, Thrombocytopenia, congenital amegakaryocytic, MIM#604498, AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3493 FANCM Zornitza Stark Gene: fancm has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3490 FANCM Zornitza Stark Classified gene: FANCM as Amber List (moderate evidence)
Mendeliome v0.3490 FANCM Zornitza Stark Gene: fancm has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3489 FANCM Zornitza Stark reviewed gene: FANCM: Rating: AMBER; Mode of pathogenicity: None; Publications: 30075111, 29895858, 28837162; Phenotypes: Spermatogenic failure 28, MIM# 618086; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3486 RBM8A Zornitza Stark Phenotypes for gene: RBM8A were changed from to Thrombocytopenia-absent radius syndrome, MIM# 274000
Mendeliome v0.3484 RBM8A Zornitza Stark reviewed gene: RBM8A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombocytopenia-absent radius syndrome, MIM# 274000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3481 RPS28 Zornitza Stark Gene: rps28 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3478 RPS28 Zornitza Stark Classified gene: RPS28 as Amber List (moderate evidence)
Mendeliome v0.3478 RPS28 Zornitza Stark Gene: rps28 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3477 RPS28 Zornitza Stark reviewed gene: RPS28: Rating: AMBER; Mode of pathogenicity: None; Publications: 24942156; Phenotypes: Diamond Blackfan anemia 15 with mandibulofacial dysostosis, MIM# 606164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3477 RPS29 Zornitza Stark Gene: rps29 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3474 RPS29 Zornitza Stark Classified gene: RPS29 as Amber List (moderate evidence)
Mendeliome v0.3474 RPS29 Zornitza Stark Gene: rps29 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3473 RPS29 Zornitza Stark reviewed gene: RPS29: Rating: AMBER; Mode of pathogenicity: None; Publications: 24829207; Phenotypes: Diamond-Blackfan anemia 13, MIM# 615909; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3464 SEC23A Zornitza Stark Gene: sec23a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3461 SEC23A Zornitza Stark Classified gene: SEC23A as Amber List (moderate evidence)
Mendeliome v0.3461 SEC23A Zornitza Stark Gene: sec23a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3458 VPS33A Zornitza Stark Gene: vps33a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3455 VPS33A Zornitza Stark Classified gene: VPS33A as Amber List (moderate evidence)
Mendeliome v0.3455 VPS33A Zornitza Stark Gene: vps33a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3454 VPS33A Zornitza Stark reviewed gene: VPS33A: Rating: AMBER; Mode of pathogenicity: None; Publications: 28013294, 27547915; Phenotypes: Mucopolysaccharidosis-plus syndrome (MIM#617303); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3450 DACT1 Natalie Tan gene: DACT1 was added
gene: DACT1 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: DACT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DACT1 were set to PMID: 28054444; 22610794; 19701191
Phenotypes for gene: DACT1 were set to ?Townes-Brocks syndrome 2 (OMIM #617466)
Review for gene: DACT1 was set to RED
Added comment: Webb et al. (2017) reported 6 affected members of a 3-generation family with ?Townes-Brocks syndrome-2, identified heterozygosity for a nonsense mutation in the DACT1 gene that segregated with disease. Clinical features include imperforate anus, rectovaginal fistula, crossed fused renal ectopia, vesicoureteral reflux, unilateral microtia, overfolded helices and cupped ears. One family member (proband's mother) with scoliosis and spina bifida occulta. Neural tube defects reported in a study of human fetuses (PMID: 22610794) and a mouse model (PMID: 19701191). Listed in Decipher v10.0 for an individual with abnormalities of (i) head or neck (ii) nervous system (iii) skeletal system. Unlike the gene SALL1 that causes Townes-Brocks syndrome 1, there is no information specifically relating to DACT1 with radial dysplasia, as these were not observed in the family with ?Townes-Brocks syndrome 2 (PMID: 28054444).
Sources: NHS GMS
Mendeliome v0.3447 POGLUT1 Zornitza Stark Phenotypes for gene: POGLUT1 were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 21 (MIM# 617232), Dowling-Degos disease 4 (MIM# 615696)
Mendeliome v0.3444 POGLUT1 Ain Roesley reviewed gene: POGLUT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27807076, 24387993; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 21 (MIM# 617232), Dowling-Degos disease 4 (MIM# 615696); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3444 SEC23A Paul De Fazio reviewed gene: SEC23A: Rating: AMBER; Mode of pathogenicity: None; Publications: 16980979, 21039434, 16980978, 27148587; Phenotypes: Craniolenticulosutural dysplasia (MIM# 607812); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3444 ARSG Zornitza Stark Added comment: Comment when marking as ready: Additional family reported with a different variant, upgrade to Amber.
Mendeliome v0.3444 ARSG Zornitza Stark Gene: arsg has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3443 ARSG Zornitza Stark Classified gene: ARSG as Amber List (moderate evidence)
Mendeliome v0.3443 ARSG Zornitza Stark Gene: arsg has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3441 FAM92A Zornitza Stark Gene: fam92a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3441 FAM92A Zornitza Stark Classified gene: FAM92A as Amber List (moderate evidence)
Mendeliome v0.3441 FAM92A Zornitza Stark Gene: fam92a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3440 FAM92A Zornitza Stark gene: FAM92A was added
gene: FAM92A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FAM92A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM92A were set to 30395363
Phenotypes for gene: FAM92A were set to Polydactyly, postaxial, type A9, MIM# 618219
Review for gene: FAM92A was set to AMBER
Added comment: Single family and a mouse model reported.
Sources: Expert list
Mendeliome v0.3431 NR0B1 Zornitza Stark Classified gene: NR0B1 as Amber List (moderate evidence)
Mendeliome v0.3431 NR0B1 Zornitza Stark Gene: nr0b1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3419 ABCD3 Zornitza Stark Gene: abcd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3416 ABCD3 Zornitza Stark Classified gene: ABCD3 as Amber List (moderate evidence)
Mendeliome v0.3416 ABCD3 Zornitza Stark Gene: abcd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3414 TBC1D32 Zornitza Stark Classified gene: TBC1D32 as Amber List (moderate evidence)
Mendeliome v0.3414 TBC1D32 Zornitza Stark Gene: tbc1d32 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3413 TBC1D32 Zornitza Stark edited their review of gene: TBC1D32: Added comment: Three families reported, but phenotypes are broad, some suggestive of ciliopathy.; Changed rating: AMBER; Changed publications: 24285566, 32573025, 32060556; Changed phenotypes: Orofaciodigital syndrome type IX, syndromic hypopituitarism
Mendeliome v0.3412 ABCD3 Crystle Lee reviewed gene: ABCD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 25168382; Phenotypes: ?Bile acid synthesis defect, congenital, 5 (MIM#616278); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3408 SPRY4 Zornitza Stark Gene: spry4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3405 SPRY4 Zornitza Stark Classified gene: SPRY4 as Amber List (moderate evidence)
Mendeliome v0.3405 SPRY4 Zornitza Stark Gene: spry4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3404 SPRY4 Zornitza Stark reviewed gene: SPRY4: Rating: AMBER; Mode of pathogenicity: None; Publications: 23643382; Phenotypes: Hypogonadotropic hypogonadism 17 with or without anosmia, MIM# 615266; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3404 KISS1 Zornitza Stark Gene: kiss1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3401 KISS1 Zornitza Stark Classified gene: KISS1 as Amber List (moderate evidence)
Mendeliome v0.3401 KISS1 Zornitza Stark Gene: kiss1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3400 KISS1 Zornitza Stark reviewed gene: KISS1: Rating: AMBER; Mode of pathogenicity: None; Publications: 22335740, 25783047, 22766261, 17563351; Phenotypes: Hypogonadotropic hypogonadism 13 with or without anosmia, MIM# 614842; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3400 INSL3 Zornitza Stark Gene: insl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3397 INSL3 Zornitza Stark Classified gene: INSL3 as Amber List (moderate evidence)
Mendeliome v0.3397 INSL3 Zornitza Stark Gene: insl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3396 INSL3 Zornitza Stark reviewed gene: INSL3: Rating: AMBER; Mode of pathogenicity: None; Publications: 12601553, 12970298, 11095425; Phenotypes: Cryptorchidism, MIM# 219050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3396 IL17RD Zornitza Stark Gene: il17rd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3393 IL17RD Zornitza Stark Classified gene: IL17RD as Amber List (moderate evidence)
Mendeliome v0.3393 IL17RD Zornitza Stark Gene: il17rd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3392 IL17RD Zornitza Stark reviewed gene: IL17RD: Rating: AMBER; Mode of pathogenicity: None; Publications: 23643382, 32389901; Phenotypes: Hypogonadotropic hypogonadism 18 with or without anosmia, MIM# 615267; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3377 GIPC1 Zornitza Stark Gene: gipc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3377 GIPC1 Zornitza Stark Classified gene: GIPC1 as Amber List (moderate evidence)
Mendeliome v0.3377 GIPC1 Zornitza Stark Gene: gipc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3376 GIPC1 Zornitza Stark gene: GIPC1 was added
gene: GIPC1 was added to Mendeliome. Sources: Literature
5'UTR, STR tags were added to gene: GIPC1.
Mode of inheritance for gene: GIPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GIPC1 were set to 32413282
Phenotypes for gene: GIPC1 were set to Oculopharyngodistal myopathy-2 (OPDM2), MIM#618940
Review for gene: GIPC1 was set to AMBER
Added comment: 19 families reported with heterozygous trinucleotide repeat expansion in the 5-prime untranslated region and onset of distal muscle weakness, mainly of the lower limbs, and/or ophthalmoplegia in the second or third decades of life. Note this is unlikely to be tractable currently by most NGS assays.
Sources: Literature
Mendeliome v0.3363 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3360 TSPYL1 Zornitza Stark Classified gene: TSPYL1 as Amber List (moderate evidence)
Mendeliome v0.3360 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3359 TSPYL1 Zornitza Stark reviewed gene: TSPYL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 15273283, 19463995, 22137496, 25449952, 16418600; Phenotypes: Sudden infant death with dysgenesis of the testes syndrome (MIM#608800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3359 PIGM Zornitza Stark Gene: pigm has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3359 PIGM Zornitza Stark Phenotypes for gene: PIGM were changed from to Glycosylphosphatidylinositol deficiency, MIM# 610293; portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events
Mendeliome v0.3356 PIGM Zornitza Stark Classified gene: PIGM as Amber List (moderate evidence)
Mendeliome v0.3356 PIGM Zornitza Stark Gene: pigm has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3349 FEZF1 Zornitza Stark Gene: fezf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3346 FEZF1 Zornitza Stark Classified gene: FEZF1 as Amber List (moderate evidence)
Mendeliome v0.3346 FEZF1 Zornitza Stark Gene: fezf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3345 ESR2 Zornitza Stark Gene: esr2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3342 ESR2 Zornitza Stark reviewed gene: ESR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29261182, 9861029, 30113650; Phenotypes: 46,XY disorder of sex development, Ovarian dysgenesis 8, MIM# 618187; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3342 PIGM Paul De Fazio reviewed gene: PIGM: Rating: AMBER; Mode of pathogenicity: None; Publications: 31445883, 16767100; Phenotypes: portal vein thrombosis, persistent absence seizures, macrocephaly, infantile-onset cerebrovascular thrombotic events; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3331 FEZF1 Elena Savva reviewed gene: FEZF1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 25192046, 32400067; Phenotypes: Hypogonadotropic hypogonadism 22, with or without anosmia 616030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3324 EXOC2 Zornitza Stark Gene: exoc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3324 EXOC2 Zornitza Stark Classified gene: EXOC2 as Amber List (moderate evidence)
Mendeliome v0.3324 EXOC2 Zornitza Stark Gene: exoc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3323 EXOC2 Zornitza Stark gene: EXOC2 was added
gene: EXOC2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: EXOC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC2 were set to 32639540
Phenotypes for gene: EXOC2 were set to Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology
Review for gene: EXOC2 was set to AMBER
Added comment: Van Bergen et al (2020 - PMID: 32639540) report on 3 individuals from 2 families, harboring biallelic EXOC2 mutations. Clinical presentation included DD, ID (severe in 2 subjects from fam1, borderline intellectual functioning in fam2), dysmorphic features and brain abnormalities. Cerebellar anomalies were common to all with a molar tooth sign observed in one (1/3). Other findings limited to subjects from one family included acquired microcephaly, congenital contractures, spastic quadriplegia (each observed 2/3). Previous investigations were in all cases non-diagnostic. WES identified biallelic EXOC2 mutations in all affected individuals. EXOC2 encodes an exocyst subunit. The latter is an octameric complex, component of the membrane transport machinery, required for tethering and fusion of vesicles at the plasma membrane. As discussed ,vesicle transport is important for the development of brain and the function of neurons and glia. Exocyst function is also important for delivery of Arl13b to the primary cilium (biallelic ARL13B mutations cause Joubert syndrome 8) and ciliogenesis. Affected subjects from a broader consanguineous family (fam1) were homozygous for a truncating variant. Fibroblast studies revealed mRNA levels compatible with NMD (further restored in presence of CHX) as well as reduced protein levels. The female belonging to the second non-consanguineous family was found to harbor 2 missense variants in trans configuration. An exocytosis defect was demonstrated in fibroblasts from individuals belonging to both families. Ciliogenesis appeared to be normal, however Arl13b localization/recruitment to the cilia was reduced compared with control cells with the defect rescued upon exogenous expression of wt EXOC2. Mutations in other genes encoding components of the exocyst complex have been previously reported in individuals with relevant phenotypes (e.g. EXOC8 in a boy with features of Joubert s. or EXOC4 in nephrotic syndrome). The authors discuss on the essential role of EXOC2 based on model organism studies (e.g. impaired neuronal membrane traffic, failure of neuronal polarization and neuromuscular junction expansion seen in Drosophila Sec5 (EXOC2) null mutants).
Sources: Expert Review
Mendeliome v0.3322 CCDC174 Zornitza Stark Gene: ccdc174 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3322 CCDC174 Zornitza Stark Classified gene: CCDC174 as Amber List (moderate evidence)
Mendeliome v0.3322 CCDC174 Zornitza Stark Gene: ccdc174 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3321 CCDC174 Zornitza Stark gene: CCDC174 was added
gene: CCDC174 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CCDC174 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC174 were set to 26358778
Phenotypes for gene: CCDC174 were set to Hypotonia, infantile, with psychomotor retardation - IHPMR, 616816
Review for gene: CCDC174 was set to AMBER
Added comment: Biallelic pathogenic CCDC174 variants cause Hypotonia, infantile, with psychomotor retardation - IHPMR (MIM 616816). Volodarsky et al [2015 - PMID: 26358778] describe 6 children from 2 unrelated families with - among others - severe hypotonia, psychomotor delay and abducens nerve palsy. All affected subjects were homozygous for a stoploss variant. Evidence from functional studies/animal model is provided supporting the role of the gene in this phenotype. Overall this gene can be considered for inclusion in the ID panel with amber rating (2 families, single founder variant, consistent phenotype, supportive studies) pending further reports.
Sources: Expert Review
Mendeliome v0.3308 SGMS2 Bryony Thompson gene: SGMS2 was added
gene: SGMS2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGMS2 were set to 30779713; 32028018
Phenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia MIM#126550
Review for gene: SGMS2 was set to GREEN
Added comment: 12 patients from 6 unrelated families with the same stopgain variant (p.Arg50*), with osteoporosis that resembles osteogenesis imperfecta. In vitro over-expression assays of the variant demonstrate protein that was completely mislocalized in the cytosolic and nuclear compartments. 2 unrelated families were heterozygous for 2 missense (p.Ile62Ser, p.Met64Arg) with bone fragility and severe short stature, and spondylometaphyseal dysplasia. In vitro assays of each variant demonstrated an enhanced rate of de novo sphingomyelin production by blocking export of a functional enzyme from the endoplasmic reticulum.
Sources: Expert list
Mendeliome v0.3303 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3300 PIP5K1C Zornitza Stark Classified gene: PIP5K1C as Amber List (moderate evidence)
Mendeliome v0.3300 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3299 PIP5K1C Zornitza Stark reviewed gene: PIP5K1C: Rating: AMBER; Mode of pathogenicity: None; Publications: 17701898; Phenotypes: Lethal congenital contractural syndrome 3, MIM# 611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3299 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3296 ERBB3 Zornitza Stark Classified gene: ERBB3 as Amber List (moderate evidence)
Mendeliome v0.3296 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3295 ERBB3 Zornitza Stark reviewed gene: ERBB3: Rating: AMBER; Mode of pathogenicity: None; Publications: 17701904, 31752936; Phenotypes: Lethal congenital contractural syndrome 2, MIM# 607598; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3295 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3292 DPM2 Zornitza Stark Classified gene: DPM2 as Amber List (moderate evidence)
Mendeliome v0.3292 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3291 DPM2 Zornitza Stark reviewed gene: DPM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23109149; Phenotypes: Congenital disorder of glycosylation, type Iu, MIM# 615042; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3290 DYSF Zornitza Stark Phenotypes for gene: DYSF were changed from to Miyoshi muscular dystrophy 1 254130; Muscular dystrophy, limb-girdle, autosomal recessive 2 253601; Myopathy, distal, with anterior tibial onset 606768
Mendeliome v0.3284 MRPS34 Zornitza Stark reviewed gene: MRPS34: Rating: GREEN; Mode of pathogenicity: None; Publications: 28777931; Phenotypes: Combined oxidative phosphorylation deficiency 32, MIM# 617664; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3284 MRPS34 Zornitza Stark Phenotypes for gene: MRPS34 were changed from to Combined oxidative phosphorylation deficiency 32, 61766
Mendeliome v0.3281 MRPS34 Elena Savva reviewed gene: MRPS34: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28777931; Phenotypes: Combined oxidative phosphorylation deficiency 32, 61766; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3281 DYSF Elena Savva reviewed gene: DYSF: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27602406; Phenotypes: Miyoshi muscular dystrophy 1 254130, Muscular dystrophy, limb-girdle, autosomal recessive 2 253601, Myopathy, distal, with anterior tibial onset 606768; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3275 PIGY Zornitza Stark Gene: pigy has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3272 PIGY Zornitza Stark Classified gene: PIGY as Amber List (moderate evidence)
Mendeliome v0.3272 PIGY Zornitza Stark Gene: pigy has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3271 MTMR14 Zornitza Stark Gene: mtmr14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3271 MTMR14 Zornitza Stark Classified gene: MTMR14 as Amber List (moderate evidence)
Mendeliome v0.3271 MTMR14 Zornitza Stark Gene: mtmr14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3267 PIGY Elena Savva reviewed gene: PIGY: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 26293662; Phenotypes: Hyperphosphatasia with mental retardation syndrome 6, MIM# 616809; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3265 MTMR14 Elena Savva reviewed gene: MTMR14: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 20400459, 20817957, 19465920, 17008356; Phenotypes: {Centronuclear myopathy, autosomal, modifier of}, MIM# 160150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3265 DNMBP Seb Lunke Marked gene: DNMBP as ready
Mendeliome v0.3265 DNMBP Seb Lunke Gene: dnmbp has been classified as Green List (High Evidence).
Mendeliome v0.3265 DNMBP Seb Lunke Classified gene: DNMBP as Green List (high evidence)
Mendeliome v0.3265 DNMBP Seb Lunke Gene: dnmbp has been classified as Green List (High Evidence).
Mendeliome v0.3264 DNMBP Seb Lunke gene: DNMBP was added
gene: DNMBP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNMBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNMBP were set to 30290152
Phenotypes for gene: DNMBP were set to congenital cataract
Review for gene: DNMBP was set to GREEN
gene: DNMBP was marked as current diagnostic
Added comment: Multiple individuals from three independent large consanguineous families with bilateral infantile cataracts. Seperate hom nonsense variants.
Sources: Literature
Mendeliome v0.3255 SFTPA1 Zornitza Stark Gene: sftpa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3252 SFTPA1 Zornitza Stark Classified gene: SFTPA1 as Amber List (moderate evidence)
Mendeliome v0.3252 SFTPA1 Zornitza Stark Gene: sftpa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3251 SFTPA1 Zornitza Stark reviewed gene: SFTPA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31601679, 30854216, 28869238, 26792177; Phenotypes: Idiopathic pulmonary fibrosis; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3251 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3251 CFAP74 Zornitza Stark Classified gene: CFAP74 as Amber List (moderate evidence)
Mendeliome v0.3251 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3250 CFAP74 Zornitza Stark gene: CFAP74 was added
gene: CFAP74 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP74 were set to 32555313
Phenotypes for gene: CFAP74 were set to Primary ciliary dyskinesia; infertility
Review for gene: CFAP74 was set to AMBER
Added comment: Two unrelated individuals with compound het missense variants reported.
Sources: Literature
Mendeliome v0.3248 LGR4 Zornitza Stark Gene: lgr4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3243 LGR4 Zornitza Stark Classified gene: LGR4 as Amber List (moderate evidence)
Mendeliome v0.3243 LGR4 Zornitza Stark Gene: lgr4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3242 RAP1GDS1 Zornitza Stark Gene: rap1gds1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3242 RAP1GDS1 Zornitza Stark Classified gene: RAP1GDS1 as Amber List (moderate evidence)
Mendeliome v0.3242 RAP1GDS1 Zornitza Stark Gene: rap1gds1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3241 KIAA1217 Zornitza Stark Gene: kiaa1217 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3241 KIAA1217 Zornitza Stark Classified gene: KIAA1217 as Amber List (moderate evidence)
Mendeliome v0.3241 KIAA1217 Zornitza Stark Gene: kiaa1217 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3240 KIAA1217 Zornitza Stark gene: KIAA1217 was added
gene: KIAA1217 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIAA1217 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIAA1217 were set to 32369272
Phenotypes for gene: KIAA1217 were set to Vertebral anomalies, syndromic and non-syndromic
Review for gene: KIAA1217 was set to AMBER
Added comment: 10 families reported, however note only 3 of the variants were absent from gnomad, inheritance not reported, most variants are missense.
Sources: Literature
Mendeliome v0.3239 LGR4 Elena Savva reviewed gene: LGR4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32493844; Phenotypes: {Bone mineral density, low, susceptibility to} 615311; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3239 RAP1GDS1 Zornitza Stark gene: RAP1GDS1 was added
gene: RAP1GDS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAP1GDS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAP1GDS1 were set to 32431071
Phenotypes for gene: RAP1GDS1 were set to Intellectual disability; dysmorphic features
Review for gene: RAP1GDS1 was set to AMBER
Added comment: Four individuals from two consanguineous families, same homozygous splice site variant detected.
Sources: Literature
Mendeliome v0.3234 HOXD10 Crystle Lee reviewed gene: HOXD10: Rating: AMBER; Mode of pathogenicity: None; Publications: 15146389, 16450407; Phenotypes: Charcot-Marie-Tooth disease, foot deformity of, Vertical talus, congenital (MIM#192950); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3222 MRAS Zornitza Stark gene: MRAS was added
gene: MRAS was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MRAS were set to 28289718
Phenotypes for gene: MRAS were set to Noonan syndrome
Review for gene: MRAS was set to AMBER
Added comment: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen.
Sources: Expert list
Mendeliome v0.3217 NRG1 Bryony Thompson Gene: nrg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3217 NRG1 Bryony Thompson Classified gene: NRG1 as Amber List (moderate evidence)
Mendeliome v0.3217 NRG1 Bryony Thompson Gene: nrg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3216 NRG1 Bryony Thompson gene: NRG1 was added
gene: NRG1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NRG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NRG1 were set to 22574178; 21706185; 28190554
Phenotypes for gene: NRG1 were set to Hirschsprung disease
Review for gene: NRG1 was set to AMBER
Added comment: Has been reported as a Hirschsprung disease susceptibility loci, with common, low-penetrance polymorphisms that contribute only partially to risk and can act as genetic modifiers. There are also two publications with rare variants reported in this gene (at least one de novo) and supporting in vitro functional assays. A null zebrafish model was also supportive of a role in Hirschsprung disease.
Sources: Expert list
Mendeliome v0.3210 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3210 CAPZA2 Zornitza Stark Classified gene: CAPZA2 as Amber List (moderate evidence)
Mendeliome v0.3210 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3202 CAPZA2 Eleanor Williams gene: CAPZA2 was added
gene: CAPZA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CAPZA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAPZA2 were set to 32338762
Phenotypes for gene: CAPZA2 were set to intellectual disability
Review for gene: CAPZA2 was set to AMBER
Added comment: PMID: 32338762 - Huang et al 2020 - report 2 unrelated families (Chinese and European) in which a de novo heterozygous variant has been identified in CAPZA2 in paediatric probands that present with global motor development delay, speech delay, intellectual disability, hypotonia. One proband had seizures at 7 months but these were controlled with medication and did not repeat. The other proband at age one had an atypical febrile seizure that was controlled without medication. Functional studies in Drosophila suggest that these variants are mild loss of function mutations but that they can act as dominant negative variants in actin polymerization in bristles.
Sources: Literature
Mendeliome v0.3202 PPP3R1 Eleanor Williams gene: PPP3R1 was added
gene: PPP3R1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPP3R1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPP3R1 were set to 32337552; 19159392
Phenotypes for gene: PPP3R1 were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: PPP3R1 was set to RED
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Mendeliome v0.3202 PLEK Eleanor Williams gene: PLEK was added
gene: PLEK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLEK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLEK were set to 32337552; 19159392
Phenotypes for gene: PLEK were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: PLEK was set to RED
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Mendeliome v0.3202 CNRIP1 Eleanor Williams gene: CNRIP1 was added
gene: CNRIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNRIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CNRIP1 were set to 32337552; 19159392
Phenotypes for gene: CNRIP1 were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: CNRIP1 was set to RED
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Mendeliome v0.3202 CCDC32 Eleanor Williams gene: CCDC32 was added
gene: CCDC32 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC32 were set to 32307552
Phenotypes for gene: CCDC32 were set to craniofacial, cardiac and neurodevelopmental anomalies
Review for gene: CCDC32 was set to AMBER
Added comment: PMID: 32307552 - Harel et al 2020 - reports 2 unrelated consanguineous families with probands with homozygous frameshift variants in CCDC32. Parents are heterozygous. Phenotype is a congenital syndrome characterized by craniofacial, cardiac and neurodevelopmental anomalies. Functional studies in zebrafish show that ccdc32 depletion impairs cilia formation and shows a role for ccdc32 in craniofacial, brain and left/right axis development.
Sources: Literature
Mendeliome v0.3199 NLRP5 Zornitza Stark Gene: nlrp5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3199 NLRP5 Zornitza Stark Classified gene: NLRP5 as Amber List (moderate evidence)
Mendeliome v0.3199 NLRP5 Zornitza Stark Gene: nlrp5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3198 NLRP5 Zornitza Stark gene: NLRP5 was added
gene: NLRP5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NLRP5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NLRP5 were set to 32222962; 31829238; 30877238
Phenotypes for gene: NLRP5 were set to Early embryonic arrest
Review for gene: NLRP5 was set to AMBER
Added comment: At least two families reported.
Sources: Literature
Mendeliome v0.3197 EMILIN1 Zornitza Stark Gene: emilin1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3197 EMILIN1 Zornitza Stark Classified gene: EMILIN1 as Amber List (moderate evidence)
Mendeliome v0.3197 EMILIN1 Zornitza Stark Gene: emilin1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3196 EXOC7 Zornitza Stark gene: EXOC7 was added
gene: EXOC7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC7 were set to 32103185
Phenotypes for gene: EXOC7 were set to brain atrophy; seizures; developmental delay; microcephaly
Review for gene: EXOC7 was set to GREEN
Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families. They showed that EXOC7, a member of the mammalian exocyst complex, is highly expressed in developing human cortex. In addition, a zebrafish model of Exoc7 deficiency recapitulates the human disorder with increased apoptosis and decreased progenitor cells during telencephalon development, suggesting that the brain atrophy in human cases reflects neuronal degeneration.
Sources: Literature
Mendeliome v0.3194 PDCD6IP Zornitza Stark gene: PDCD6IP was added
gene: PDCD6IP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDCD6IP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCD6IP were set to 32286682
Phenotypes for gene: PDCD6IP were set to Microcephaly; intellectual disability
Review for gene: PDCD6IP was set to AMBER
Added comment: One consanguineous family with 2 affected sibs with primary microcephaly (-4SD), intellectual disability and short stature (-5/6SD), and homozygous frameshift variant in PDCD6IP. The homozygous variant was confirmed in both affected sibs, while the four healthy siblings and parents were heterozygous. The clinical features observed in the patients were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies.
Sources: Literature
Mendeliome v0.3193 NME5 Zornitza Stark Gene: nme5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3193 NME5 Zornitza Stark Classified gene: NME5 as Amber List (moderate evidence)
Mendeliome v0.3193 NME5 Zornitza Stark Gene: nme5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3192 NME5 Zornitza Stark gene: NME5 was added
gene: NME5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NME5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NME5 were set to 32185794
Phenotypes for gene: NME5 were set to Primary ciliary dyskinesia
Review for gene: NME5 was set to AMBER
Added comment: One patient with PCD with situs solitus, with radial spokes (RS) and central pair (CP) defects. Patient had a homozygous nonsense variant in NME5, with parents as carriers. Morpholino knockdown of nme5 in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy.
Sources: Literature
Mendeliome v0.3189 EMILIN1 Naomi Baker changed review comment from: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature; to: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature
Mendeliome v0.3189 EMILIN1 Naomi Baker gene: EMILIN1 was added
gene: EMILIN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EMILIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EMILIN1 were set to PMID: 31978608; 26462740.
Phenotypes for gene: EMILIN1 were set to peripheral neuropathy
Penetrance for gene: EMILIN1 were set to unknown
Review for gene: EMILIN1 was set to AMBER
Added comment: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature
Mendeliome v0.3186 SP6 Zornitza Stark Gene: sp6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3186 SP6 Zornitza Stark Classified gene: SP6 as Amber List (moderate evidence)
Mendeliome v0.3186 SP6 Zornitza Stark Gene: sp6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3185 SP6 Eleanor Williams gene: SP6 was added
gene: SP6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SP6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SP6 were set to 32167558; 18156176; 18297738; 22676574
Phenotypes for gene: SP6 were set to hypoplastic amelogenesis imperfecta
Review for gene: SP6 was set to AMBER
Added comment: PMID: 32167558 - Smith et al 2020 - report a 2 bp variant c.817_818GC>AA in SP6 in a Caucasian family with autosomal dominant hypoplastic AI which results in a missense change. Report that mice and rat knockouts also show a dental phenotype (PMID: 18156176, 18297738, 22676574 )
Sources: Literature
Mendeliome v0.3182 SKIV2L Sarah Leigh reviewed gene: SKIV2L: Rating: AMBER; Mode of pathogenicity: None; Publications: 29334452; Phenotypes: Intellectual disability; Mode of inheritance: None
Mendeliome v0.3166 ESR2 Bryony Thompson Classified gene: ESR2 as Amber List (moderate evidence)
Mendeliome v0.3166 ESR2 Bryony Thompson Gene: esr2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3157 AXL Bryony Thompson Gene: axl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3157 AXL Bryony Thompson Classified gene: AXL as Amber List (moderate evidence)
Mendeliome v0.3157 AXL Bryony Thompson Gene: axl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3156 AXL Bryony Thompson gene: AXL was added
gene: AXL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AXL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AXL were set to 18787040; 24476074
Phenotypes for gene: AXL were set to Kallman syndrome; normosmic idiopathic hypogonadotropic hypogonadism
Review for gene: AXL was set to AMBER
Added comment: Axl null mice had delayed first oestrus and persistently abnormal oestrous cyclicality compared with wild-type controls. Only a single study reported screening human cases. In a screen of 104 probands with KS or nIHH, four heterozygous AXL mutations were identified in two KS and two nIHH unrelated subjects (two males and two females). Three of the variants appear to be too common in gnomAD v2.1 given the reported prevalence of KS reported in GeneReviews (1:30,000 in males and 1:125,000 in females): c.587-6C>T (normal splicing in RNA studies, NFE AF 0.0001472), p.Q361P (NFE 0.002560), p.L50F (AJ 0.004405). The other variant p.S202C (4 hets, 1 female in gnomAD v2.1) is rare enough in gnomAD for a dominant disorder. In vitro functional assays were conducted and p.S202C had an significant effect on function, but so did the more common variant p.Q361P.
Sources: Literature
Mendeliome v0.3147 PHOX2A Zornitza Stark Gene: phox2a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3144 PHOX2A Zornitza Stark Classified gene: PHOX2A as Amber List (moderate evidence)
Mendeliome v0.3144 PHOX2A Zornitza Stark Gene: phox2a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3143 PHOX2A Elena Savva reviewed gene: PHOX2A: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 11600883, 18323871; Phenotypes: Fibrosis of extraocular muscles, congenital, 2 602078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3089 DCAF8 Bryony Thompson Classified gene: DCAF8 as Amber List (moderate evidence)
Mendeliome v0.3089 DCAF8 Bryony Thompson Gene: dcaf8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3088 DCAF8 Bryony Thompson gene: DCAF8 was added
gene: DCAF8 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DCAF8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DCAF8 were set to 24500646
Phenotypes for gene: DCAF8 were set to Giant axonal neuropathy 2, autosomal dominant MIM#610100
Review for gene: DCAF8 was set to AMBER
Added comment: A single large family segregating a missense variant and in vitro functional assays demonstrating the variant reduces the association of DCAF8 and DDB1, which is important in Cul4-ubiquitin E3 function
Sources: Expert list
Mendeliome v0.3074 RYR3 Zornitza Stark Gene: ryr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3074 RYR3 Zornitza Stark Classified gene: RYR3 as Amber List (moderate evidence)
Mendeliome v0.3074 RYR3 Zornitza Stark Gene: ryr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3073 RYR3 Zornitza Stark gene: RYR3 was added
gene: RYR3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RYR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RYR3 were set to 29498452; 32451403; 31230720
Phenotypes for gene: RYR3 were set to Nemaline myopathy; fetal akinesia; arthrogryposis
Review for gene: RYR3 was set to AMBER
Added comment: One family reported with nemaline myopathy and other cases reported as part of large fetal akinesia/arthrogryposis discovery cohorts reporting multiple novel gene candidates.
Sources: Expert list
Mendeliome v0.3065 PLAG1 Zornitza Stark Gene: plag1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3062 PLAG1 Zornitza Stark Classified gene: PLAG1 as Amber List (moderate evidence)
Mendeliome v0.3062 PLAG1 Zornitza Stark Gene: plag1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3061 PLAG1 Zornitza Stark reviewed gene: PLAG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28796236, 29913240; Phenotypes: Silver-Russell syndrome, MIM#618907; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3049 PSMB1 Zornitza Stark Marked gene: PSMB1 as ready
Mendeliome v0.3049 PSMB1 Zornitza Stark Gene: psmb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3049 PSMB1 Zornitza Stark Classified gene: PSMB1 as Amber List (moderate evidence)
Mendeliome v0.3049 PSMB1 Zornitza Stark Gene: psmb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3048 PSMB1 Zornitza Stark gene: PSMB1 was added
gene: PSMB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB1 were set to 32129449
Phenotypes for gene: PSMB1 were set to Intellectual disability; microcephaly
Review for gene: PSMB1 was set to AMBER
Added comment: Two siblings reported with a homozygous missense variant in this gene; supportive experimental evidence including zebrafish model.
Sources: Literature
Mendeliome v0.3044 C16orf62 Zornitza Stark changed review comment from: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475).
Sources: Expert list; to: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475;31712251).
Sources: Expert list
Mendeliome v0.3044 EWSR1 Seb Lunke Gene: ewsr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3041 EWSR1 Seb Lunke Classified gene: EWSR1 as Amber List (moderate evidence)
Mendeliome v0.3041 EWSR1 Seb Lunke Gene: ewsr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3040 EWSR1 Seb Lunke reviewed gene: EWSR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 29731676, 22454397; Phenotypes: Amyotrophic lateral sclerosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3038 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3038 C16orf62 Zornitza Stark Classified gene: C16orf62 as Amber List (moderate evidence)
Mendeliome v0.3038 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3037 C16orf62 Zornitza Stark gene: C16orf62 was added
gene: C16orf62 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: C16orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C16orf62 were set to 25434475
Phenotypes for gene: C16orf62 were set to 3C/Ritscher-Schinzel-like syndrome
Review for gene: C16orf62 was set to AMBER
Added comment: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475).
Sources: Expert list
Mendeliome v0.3018 PERP Zornitza Stark Gene: perp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3018 PERP Zornitza Stark Classified gene: PERP as Amber List (moderate evidence)
Mendeliome v0.3018 PERP Zornitza Stark Gene: perp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3017 PERP Zornitza Stark gene: PERP was added
gene: PERP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PERP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PERP were set to 31898316
Phenotypes for gene: PERP were set to Erythrokeratoderma, no OMIM # yet
Review for gene: PERP was set to AMBER
Added comment: One extended multiplex consanguineous family with Erythrokeratoderma (striking similarity to that observed in Perp −/− mice), and a novel homozygous variant (c.466G>A; p.Gly156Arg) in PERP that fully segregated with the phenotype. Functional analysis of patient‐ and control‐derived keratinocytes revealed a deleterious effect of the identified variant on the intracellular localization of PERP. A previous report showed that PERP mutation causes a dominant form of keratoderma but a single patient in that report with a homozygous variant in PERP suggests that recessive inheritance is also possible.
Sources: Literature
Mendeliome v0.3014 DSCR3 Zornitza Stark gene: DSCR3 was added
gene: DSCR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DSCR3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DSCR3 were set to 31845315
Phenotypes for gene: DSCR3 were set to Intellectual disability, no OMIM # yet
Review for gene: DSCR3 was set to RED
Added comment: 1 family/2 cousins with cognitive impairment, growth failure, skeletal abnormalities, and distinctive facial features. Both shared the homozygous nonsense variant c.178G>T (p.Glu60*) in the VPS26C gene. This gene encodes VPS26C, a member of the retriever integral membrane protein recycling pathway. The nature of the variant which is predicted to result in loss‐of‐function, expression studies revealing significant reduction in the mutant transcript, and the co‐segregation of the homozygous variant with the phenotype in two affected individuals.
Sources: Literature
Mendeliome v0.2996 ARL13B Zornitza Stark edited their review of gene: ARL13B: Added comment: Eight families reported in the literature. Many are homozygous missense variants in consanguineous families with no further supporting evidence, but sufficient number have functional evidence at protein level. Gene has appropriate tissue expression. Zebrafish model: curved tails and cystic kidneys. Hennin mouse model discovered in ENU mutagenesis screen: has polydactyly, ciliary defect, and much more severe neurological phenotype (neural tube defect).; Changed publications: 18674751, 25138100, 26092869, 27894351, 29255182, 17488627
Mendeliome v0.2996 DNAL1 Zornitza Stark Gene: dnal1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2993 DNAL1 Zornitza Stark Classified gene: DNAL1 as Amber List (moderate evidence)
Mendeliome v0.2993 DNAL1 Zornitza Stark Gene: dnal1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2992 DNAL1 Zornitza Stark reviewed gene: DNAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21496787; Phenotypes: Ciliary dyskinesia, primary, 16, MIM# 614017; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2992 DNAH8 Zornitza Stark Gene: dnah8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2989 DNAH8 Zornitza Stark Classified gene: DNAH8 as Amber List (moderate evidence)
Mendeliome v0.2989 DNAH8 Zornitza Stark Gene: dnah8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2988 DNAH8 Zornitza Stark reviewed gene: DNAH8: Rating: AMBER; Mode of pathogenicity: None; Publications: 31178125, 24307375; Phenotypes: Asthenozoospermia, primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2985 DNAH6 Zornitza Stark Gene: dnah6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2985 DNAH6 Zornitza Stark Classified gene: DNAH6 as Amber List (moderate evidence)
Mendeliome v0.2985 DNAH6 Zornitza Stark Gene: dnah6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2978 HIST1H4J Zornitza Stark Gene: hist1h4j has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2978 HIST1H4J Zornitza Stark Classified gene: HIST1H4J as Amber List (moderate evidence)
Mendeliome v0.2978 HIST1H4J Zornitza Stark Gene: hist1h4j has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2977 HIST1H4J Zornitza Stark gene: HIST1H4J was added
gene: HIST1H4J was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIST1H4J was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIST1H4J were set to 31804630
Phenotypes for gene: HIST1H4J were set to microcephaly; intellectual disability; dysmorphic features
Review for gene: HIST1H4J was set to AMBER
Added comment: Single case report but with functional evidence in zebrafish and phenotypic similarity to other HIST1H4C phenotype
Sources: Literature
Mendeliome v0.2970 EFEMP1 Zornitza Stark Phenotypes for gene: EFEMP1 were changed from to Doyne honeycomb degeneration of retina, MIM# 126600; EFEMP1-related connective tissue disorder
Mendeliome v0.2966 EFEMP1 Zornitza Stark reviewed gene: EFEMP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32006683, 31792352; Phenotypes: Doyne honeycomb degeneration of retina, MIM# 126600, EFEMP1-related connective tissue disorder; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2960 SCYL2 Zornitza Stark Gene: scyl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2960 SCYL2 Zornitza Stark Classified gene: SCYL2 as Amber List (moderate evidence)
Mendeliome v0.2960 SCYL2 Zornitza Stark Gene: scyl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2959 SCYL2 Zornitza Stark gene: SCYL2 was added
gene: SCYL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SCYL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCYL2 were set to 31960134; 26203146
Phenotypes for gene: SCYL2 were set to Arthrogryposis multiplex congenita (AMC); Zain syndrome
Review for gene: SCYL2 was set to AMBER
Added comment: Two unrelated families reported with AMC, variable other features including microcephaly.
Sources: Literature
Mendeliome v0.2958 CNP Seb Lunke Gene: cnp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2958 CNP Seb Lunke Classified gene: CNP as Amber List (moderate evidence)
Mendeliome v0.2958 CNP Seb Lunke Gene: cnp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2956 VWA3B Bryony Thompson Classified gene: VWA3B as Amber List (moderate evidence)
Mendeliome v0.2956 VWA3B Bryony Thompson Gene: vwa3b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2955 VWA3B Bryony Thompson gene: VWA3B was added
gene: VWA3B was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: VWA3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VWA3B were set to 26157035
Phenotypes for gene: VWA3B were set to Spinocerebellar ataxia, autosomal recessive 22 MIM#616948
Review for gene: VWA3B was set to AMBER
Added comment: A homozygous missense variant was identified in 3 brothers from a single consanguineous Japanese family with autosomal recessive cerebellar ataxia. Transfection of the mutant VWA3B protein into several different cultured cell lines resulted in decreased cell viability.
Sources: Expert list
Mendeliome v0.2953 SOX6 Paul De Fazio changed review comment from: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me (paper says 19 individuals from 17 families). 12 were de novo.
Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome. Paper says 19 individuals from 17 families. 12 were de novo.
Sources: Literature
Mendeliome v0.2952 SOX6 Paul De Fazio changed review comment from: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me (paper says 19 individuals from 17 families). 12 were de novo.
Sources: Literature
Mendeliome v0.2952 PLD3 Bryony Thompson Classified gene: PLD3 as Amber List (moderate evidence)
Mendeliome v0.2952 PLD3 Bryony Thompson Gene: pld3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2950 PLD3 Bryony Thompson gene: PLD3 was added
gene: PLD3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PLD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLD3 were set to 29053796; 30312375; 30312384
Phenotypes for gene: PLD3 were set to Spinocerebellar ataxia 46 MIM#617770
Review for gene: PLD3 was set to AMBER
Added comment: A heterozygous missense was identified in 8 affected members of a single family with spinocerebellar ataxia, and supporting in vitro functional assays.
Sources: Expert list
Mendeliome v0.2949 SOX6 Paul De Fazio changed review comment from: 6 LoF and 4 missense variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature
Mendeliome v0.2947 KIF3B Zornitza Stark Gene: kif3b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2946 KIF3B Zornitza Stark Classified gene: KIF3B as Amber List (moderate evidence)
Mendeliome v0.2946 KIF3B Zornitza Stark Gene: kif3b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2945 KIF3B Zornitza Stark edited their review of gene: KIF3B: Changed rating: AMBER
Mendeliome v0.2943 KIF3B Paul De Fazio gene: KIF3B was added
gene: KIF3B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KIF3B were set to hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly
Review for gene: KIF3B was set to AMBER
Added comment: 2 families reported with missense variants, one de novo and one segregating in a six-generation pedigree. Functional studies in zebrafish showed the variants result in impaired rhodopsin trafficking.
Sources: Literature
Mendeliome v0.2943 SOX6 Paul De Fazio gene: SOX6 was added
gene: SOX6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SOX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX6 were set to 32442410
Phenotypes for gene: SOX6 were set to ADHD; Craniosynostosis; Osteochondromas
Added comment: 6 LoF and 4 missense variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature
Mendeliome v0.2943 CNP Kristin Rigbye gene: CNP was added
gene: CNP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNP were set to 32128616; 12590258
Phenotypes for gene: CNP were set to Hypomyelinating leukodystrophy
Review for gene: CNP was set to AMBER
Added comment: Single consanguineous family described with homozygous missense in affected child (additional two affected deceased offspring unavailable for testing; healthy carrier parents and sibling).
Loss of protein by Western blot and defect in F-actin structure and organization observed in patient fibroblasts.
Deficiency of CNP in mouse has previously been shown to cause a lethal white matter neurodegenerative phenotype (PMID: 12590258), similar to the phenotype observed in this family.
Sources: Literature
Mendeliome v0.2943 RBM7 Bryony Thompson Classified gene: RBM7 as Amber List (moderate evidence)
Mendeliome v0.2943 RBM7 Bryony Thompson Gene: rbm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2942 RBM7 Bryony Thompson gene: RBM7 was added
gene: RBM7 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RBM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBM7 were set to 27193168
Phenotypes for gene: RBM7 were set to SMA-like spinal motor neuropathy; dHMN/dSMA
Review for gene: RBM7 was set to AMBER
Added comment: Single case with a homozygote variant, with functional assays in patient fibroblasts. Also, supporting zebrafish model.
Sources: Expert list
Mendeliome v0.2932 DNAH6 Elena Savva gene: DNAH6 was added
gene: DNAH6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNAH6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH6 were set to PMID: 26918822
Phenotypes for gene: DNAH6 were set to Heterotaxy, Azoospermia
Review for gene: DNAH6 was set to AMBER
Added comment: PMID: 26918822 - zebrafish model has disrupted motile cilia and cilia length, with some body axis defects within embryos. Transfected human cells also had defective motile cilia and cilia width.
Two patients with heterotaxy, one homozygous (missense), the other heterozygous (missense), but the heterozygous carrier has an additional known PCD mutation in DNA1.

Summary: 1 convincing patient with animal model
Sources: Literature
Mendeliome v0.2927 PRKAG3 Bryony Thompson Classified gene: PRKAG3 as Amber List (moderate evidence)
Mendeliome v0.2927 PRKAG3 Bryony Thompson Gene: prkag3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2926 PRKAG3 Bryony Thompson reviewed gene: PRKAG3: Rating: AMBER; 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: 17878938, 10818001; Phenotypes: increased glycogen content in skeletal muscle; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2925 ANO5 Zornitza Stark Phenotypes for gene: ANO5 were changed from to Gnathodiaphyseal dysplasia MIM#166260; Miyoshi muscular dystrophy 3 MIM#613319; Muscular dystrophy, limb-girdle, autosomal recessive 12 MIM#611307
Mendeliome v0.2918 ANO5 Bryony Thompson reviewed gene: ANO5: Rating: GREEN; Mode of pathogenicity: None; Publications: 32112655; Phenotypes: Gnathodiaphyseal dysplasia MIM#166260, Miyoshi muscular dystrophy 3 MIM#613319, Muscular dystrophy, limb-girdle, autosomal recessive 12 MIM#611307; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2906 SNRNP200 Ain Roesley changed review comment from: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD)

PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling

PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA)

PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister

PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.4Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo; to: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD)

PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling

PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA)

PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister

PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.1Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo
Mendeliome v0.2906 SNRNP200 Ain Roesley changed review comment from: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD)

PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling

PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA)

PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister

PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.1Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo; to: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD)

PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling

PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA)

PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister

PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.4Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo
Mendeliome v0.2889 ARL3 Bryony Thompson gene: ARL3 was added
gene: ARL3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARL3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ARL3 were set to 30269812; 16565502; 26964041; 30932721
Phenotypes for gene: ARL3 were set to Joubert syndrome 35 MIM#618161; Retinitis pigmentosa 83 MIM#618173
Review for gene: ARL3 was set to GREEN
Added comment: 4 patients from 2 unrelated consanguineous families with a phenotype resembling Joubert syndrome with homozygous missense mutations affecting the same residue (R149C, R149H), and supporting in vitro functional assays. All reported cases had rod-cone dystrophy. An Arl3 null mouse model has a ciliary disease phenotype affecting the kidney, biliary tract, pancreas, and retina.
Two unrelated families with retinitis pigmentosa segregating the same heterozygous missense variant (Y90C).
Sources: Expert list
Mendeliome v0.2883 CEP19 Bryony Thompson Classified gene: CEP19 as Amber List (moderate evidence)
Mendeliome v0.2883 CEP19 Bryony Thompson Gene: cep19 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2882 CEP19 Bryony Thompson gene: CEP19 was added
gene: CEP19 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CEP19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP19 were set to 29127258; 24268657
Phenotypes for gene: CEP19 were set to Morbid obesity and spermatogenic failure MIM#615703
Review for gene: CEP19 was set to AMBER
Added comment: A consanguineous Arab family with morbid obesity and infertility with a homozygous predicted null variant, and a mouse model that recapitulates the phenotype. Another homozygous variant has been identified in a consanguineous Bardet Beidl syndrome.
Sources: Literature
Mendeliome v0.2881 DALRD3 Zornitza Stark Gene: dalrd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2881 DALRD3 Zornitza Stark Classified gene: DALRD3 as Amber List (moderate evidence)
Mendeliome v0.2881 DALRD3 Zornitza Stark Gene: dalrd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2880 DALRD3 Zornitza Stark gene: DALRD3 was added
gene: DALRD3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DALRD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DALRD3 were set to 32427860
Phenotypes for gene: DALRD3 were set to Epileptic encephalopathy
Review for gene: DALRD3 was set to AMBER
Added comment: Two individuals reported with same homozygous nonsense variant, functional data.
Sources: Literature
Mendeliome v0.2860 JARID2 Zornitza Stark Gene: jarid2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2860 JARID2 Zornitza Stark Classified gene: JARID2 as Amber List (moderate evidence)
Mendeliome v0.2860 JARID2 Zornitza Stark Gene: jarid2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2859 JARID2 Zornitza Stark gene: JARID2 was added
gene: JARID2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: JARID2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JARID2 were set to 23294540
Phenotypes for gene: JARID2 were set to Intellectual disability
Review for gene: JARID2 was set to AMBER
Added comment: Emerging evidence that haploinsufficiency causes neurodevelopmental phenotypes, mostly based on CNV data to date.
Sources: Expert Review
Mendeliome v0.2857 ADIPOR1 Zornitza Stark Gene: adipor1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2854 ADIPOR1 Zornitza Stark Classified gene: ADIPOR1 as Amber List (moderate evidence)
Mendeliome v0.2854 ADIPOR1 Zornitza Stark Gene: adipor1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2853 ADIPOR1 Zornitza Stark reviewed gene: ADIPOR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27655171, 26662040; Phenotypes: Retinitis pigmentosa; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2848 CLCC1 Zornitza Stark Gene: clcc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2848 CLCC1 Bryony Thompson Classified gene: CLCC1 as Amber List (moderate evidence)
Mendeliome v0.2848 CLCC1 Bryony Thompson Gene: clcc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2847 CLCC1 Bryony Thompson gene: CLCC1 was added
gene: CLCC1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CLCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLCC1 were set to 30157172
Phenotypes for gene: CLCC1 were set to Retinitis pigmentosa 32
Review for gene: CLCC1 was set to AMBER
Added comment: A presumptive Pakastani founder mutation (c.75C>A, p.D25E) was identified in 8 consanguineous arRP families. A knockout zebrafish model and a Clcc1 +/- mouse model had a supporting retinal phenotype.
Sources: Expert list
Mendeliome v0.2846 B9D1 Zornitza Stark Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2843 B9D1 Zornitza Stark Classified gene: B9D1 as Amber List (moderate evidence)
Mendeliome v0.2843 B9D1 Zornitza Stark Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2842 B9D1 Zornitza Stark edited their review of gene: B9D1: Changed rating: AMBER
Mendeliome v0.2839 ZNF423 Zornitza Stark Classified gene: ZNF423 as Amber List (moderate evidence)
Mendeliome v0.2839 ZNF423 Zornitza Stark Gene: znf423 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2838 ZNF423 Zornitza Stark edited their review of gene: ZNF423: Changed rating: AMBER
Mendeliome v0.2827 PDXK Zornitza Stark Gene: pdxk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2826 PDXK Zornitza Stark Classified gene: PDXK as Amber List (moderate evidence)
Mendeliome v0.2826 PDXK Zornitza Stark Gene: pdxk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2825 PDXK Zornitza Stark reviewed gene: PDXK: Rating: AMBER; Mode of pathogenicity: None; Publications: 31187503; Phenotypes: Axonal polyneuropathy, optic atrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2792 CEP112 Bryony Thompson Classified gene: CEP112 as Amber List (moderate evidence)
Mendeliome v0.2792 CEP112 Bryony Thompson Gene: cep112 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2791 CEP112 Bryony Thompson gene: CEP112 was added
gene: CEP112 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CEP112 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP112 were set to 31654588
Phenotypes for gene: CEP112 were set to Acephalic spermatozoa; infertility
Review for gene: CEP112 was set to AMBER
Added comment: Two unrelated cases reported with acephalic spermatozoa, one case with a homozygous nonsense variant and the other case with biallelic missense variants. CEP112 expression was significantly reduced in one of the cases, suggesting loss of function as a mechanism of disease.
Sources: Literature
Mendeliome v0.2787 TOMM70 Zornitza Stark Gene: tomm70 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2787 TOMM70 Zornitza Stark Classified gene: TOMM70 as Amber List (moderate evidence)
Mendeliome v0.2787 TOMM70 Zornitza Stark Gene: tomm70 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2786 TOMM70 Zornitza Stark gene: TOMM70 was added
gene: TOMM70 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TOMM70 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TOMM70 were set to 31907385; 32356556
Phenotypes for gene: TOMM70 were set to Severe anaemia, lactic acidosis, developmental delay; White matter abnormalities, developmental delay, regression, movement disorder
Review for gene: TOMM70 was set to AMBER
Added comment: TOM70 is a member of the TOM complex that transports cytosolic proteins into mitochondria.
Bi-allelic disease: one individual reported with compound heterozygous variants in TOMM70 [c.794C>T (p.T265M) and c.1745C>T (p.A582V)]. Clinical features included severe anaemia, lactic acidosis, and developmental delay. Some functional data: in vitro cell model compensatory experiments.
Monoallelic disease: de novo mono allelic variants in the C-terminal region of TOMM70 reported in two individuals. While both individuals exhibited shared symptoms including hypotonia, hyperreflexia, ataxia, dystonia, and significant white matter abnormalities, there were differences between the two individuals, most prominently the age of symptom onset, with one experiencing episodes of regression. Some functional data.
Sources: Expert list
Mendeliome v0.2777 GAS2L2 Zornitza Stark Gene: gas2l2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2774 GAS2L2 Zornitza Stark Classified gene: GAS2L2 as Amber List (moderate evidence)
Mendeliome v0.2774 GAS2L2 Zornitza Stark Gene: gas2l2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2773 GAS2L2 Zornitza Stark reviewed gene: GAS2L2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30665704; Phenotypes: Ciliary dyskinesia, primary, 41 (MIM # 618449); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2767 UGDH Zornitza Stark gene: UGDH was added
gene: UGDH was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGDH were set to 32001716
Phenotypes for gene: UGDH were set to Epileptic encephalopathy, early infantile, 84 - MIM #618792
Review for gene: UGDH was set to GREEN
Added comment: 36 individuals with biallelic UGDH pathogenic variants reported. The phenotype corresponded overall to a developmental epileptic encephalopathy with hypotonia, feeding difficulties, severe global DD, moderate or commonly severe ID in all. Hypotonia and motor disorder (incl. spasticity, dystonia, ataxia, chorea, etc) often occurred prior to the onset of seizures. A single individual did not present seizures and 2 sibs had only seizures in the setting of fever. There were no individuals with biallelic pLoF variants identified. Parental/sib studies were all compatible with AR inheritance mode.

UGDH encodes the enzyme UDP-glucose dehydrogenase which converts UDP-glucose to UDP-glucuronate, the latter being a critical component of the glycosaminoglycans, hyaluronan, chondroitin sulfate, and heparan sulfate. Patient fibroblast and biochemical assays suggested a LoF effect of variants leading to impairment of UGDH stability, oligomerization or enzymatic activity (decreased UGDH-catalyzed reduction of NAD+ to NADH / hyaluronic acid production which requires UDP-glucuronate).

Attempts to model the disorder using an already developped zebrafish model (for a hypomorphic LoF allele) were unsuccessful as fish did not exhibit seizures spontaneously or upon induction with PTZ. Modelling of the disorder in vitro using patient-derived cerebral organoids demonstrated smaller organoids due to reduced number of proliferating neural progenitors
Sources: Literature
Mendeliome v0.2757 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2754 DNAJB13 Zornitza Stark Classified gene: DNAJB13 as Amber List (moderate evidence)
Mendeliome v0.2754 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2753 DNAJB13 Zornitza Stark reviewed gene: DNAJB13: Rating: AMBER; Mode of pathogenicity: None; Publications: 27486783; Phenotypes: Ciliary dyskinesia, primary, 34, MIM# 617091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2747 TTC25 Zornitza Stark Gene: ttc25 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2744 TTC25 Zornitza Stark Classified gene: TTC25 as Amber List (moderate evidence)
Mendeliome v0.2744 TTC25 Zornitza Stark Gene: ttc25 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2743 TTC25 Zornitza Stark reviewed gene: TTC25: Rating: AMBER; Mode of pathogenicity: None; Publications: 27486780; Phenotypes: Ciliary dyskinesia, primary, 35 (MIM#617092); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2738 CDX2 Zornitza Stark Gene: cdx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2735 CDX2 Zornitza Stark Classified gene: CDX2 as Amber List (moderate evidence)
Mendeliome v0.2735 CDX2 Zornitza Stark Gene: cdx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2734 CDX2 Zornitza Stark reviewed gene: CDX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29177441; Phenotypes: Persistent cloaca; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2734 TAPT1 Zornitza Stark Gene: tapt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2731 TAPT1 Zornitza Stark Classified gene: TAPT1 as Amber List (moderate evidence)
Mendeliome v0.2731 TAPT1 Zornitza Stark Gene: tapt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2730 TAPT1 Zornitza Stark reviewed gene: TAPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26365339; Phenotypes: Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2730 CCDC28B Zornitza Stark Classified gene: CCDC28B as Amber List (moderate evidence)
Mendeliome v0.2730 CCDC28B Zornitza Stark Gene: ccdc28b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2729 CCDC28B Zornitza Stark edited their review of gene: CCDC28B: Added comment: PMID: 32139166 - Single family with Joubert syndrome. Patient was homozygous for a missense, with polydactyly, severe ID, and the molar tooth sign observed in MRI. Sibling fetus MRI showed vermis hypoplasia, and was also homozygous for the variant. Parents confirmed unaffected carriers. Knockdown of CCDC28B in human TERT retinal pigment epithelial cells reduced both the number and length of cilia 430C-T variant is postulated to be a modifier of BBS.; Changed rating: AMBER; Changed publications: 32139166; Changed phenotypes: {Bardet-Biedl syndrome 1, modifier of}, MIM#209900, Joubert syndrome
Mendeliome v0.2700 ATP5E Zornitza Stark Gene: atp5e has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2697 ATP5E Zornitza Stark Classified gene: ATP5E as Amber List (moderate evidence)
Mendeliome v0.2697 ATP5E Zornitza Stark Gene: atp5e has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2696 ATP5E Zornitza Stark reviewed gene: ATP5E: Rating: AMBER; Mode of pathogenicity: None; Publications: 20566710, 27626380, 20026007; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 MIM#614053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2693 ATP5A1 Zornitza Stark Gene: atp5a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2693 ATP5A1 Zornitza Stark Phenotypes for gene: ATP5A1 were changed from to Combined oxidative phosphorylation deficiency 22 616045; Mitochondrial complex V (ATP synthase) deficiency nuclear type 4, 615228
Mendeliome v0.2690 ATP5A1 Zornitza Stark Classified gene: ATP5A1 as Amber List (moderate evidence)
Mendeliome v0.2690 ATP5A1 Zornitza Stark Gene: atp5a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2689 ATP5A1 Zornitza Stark reviewed gene: ATP5A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23599390; Phenotypes: Combined oxidative phosphorylation deficiency 22 616045, Mitochondrial complex V (ATP synthase) deficiency nuclear type 4, 615228; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2686 CD4 Zornitza Stark reviewed gene: CD4: Rating: AMBER; Mode of pathogenicity: None; Publications: 31781092; Phenotypes: Absence of CD4+ T cells, exuberant, relapsing, treatment-refractory warts; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2685 TNK2 Zornitza Stark Gene: tnk2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2682 TNK2 Zornitza Stark Classified gene: TNK2 as Amber List (moderate evidence)
Mendeliome v0.2682 TNK2 Zornitza Stark Gene: tnk2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2680 TNK2 Elena Savva reviewed gene: TNK2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID 27977884, 23686771, 31517310; Phenotypes: late onset infantile epilepsy, Mayer-Rokitansky-Küster-Hauser syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2675 RC3H1 Zornitza Stark Gene: rc3h1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2675 RC3H1 Zornitza Stark Classified gene: RC3H1 as Amber List (moderate evidence)
Mendeliome v0.2675 RC3H1 Zornitza Stark Gene: rc3h1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2675 RC3H1 Zornitza Stark Classified gene: RC3H1 as Amber List (moderate evidence)
Mendeliome v0.2675 RC3H1 Zornitza Stark Gene: rc3h1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2674 RC3H1 Zornitza Stark edited their review of gene: RC3H1: Changed rating: AMBER; Changed publications: 31636267, 15917799
Mendeliome v0.2669 ITPKB Zornitza Stark gene: ITPKB was added
gene: ITPKB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ITPKB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITPKB were set to 31987846
Phenotypes for gene: ITPKB were set to Severe combined immunodeficiency, absent T cells, present B cells and NK cells
Review for gene: ITPKB was set to RED
Added comment: Single individual with homozygous bi-allelic LoF variant reported.
Sources: Literature
Mendeliome v0.2668 PSMB10 Zornitza Stark Marked gene: PSMB10 as ready
Mendeliome v0.2668 PSMB10 Zornitza Stark Gene: psmb10 has been classified as Red List (Low Evidence).
Mendeliome v0.2668 PSMB10 Zornitza Stark gene: PSMB10 was added
gene: PSMB10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMB10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB10 were set to 31783057
Phenotypes for gene: PSMB10 were set to Autoinflammatory syndrome
Review for gene: PSMB10 was set to RED
Added comment: PSMB10 is part of the immunoproteasome, and other components cause auto inflammatory disorders. Single individual with homozygous missense variant reported.
Sources: Literature
Mendeliome v0.2660 NOS2 Zornitza Stark reviewed gene: NOS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 12433515, 31995689; Phenotypes: {Malaria, resistance to} 611162, Disseminated CMV disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2655 EMX2 Zornitza Stark Gene: emx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2652 EMX2 Zornitza Stark Classified gene: EMX2 as Amber List (moderate evidence)
Mendeliome v0.2652 EMX2 Zornitza Stark Gene: emx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2651 EMX2 Zornitza Stark reviewed gene: EMX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 8528262, 9359037, 9153481, 9153481, 18409201; Phenotypes: Schizencephaly, MIM# 269160; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2646 MN1 Zornitza Stark Phenotypes for gene: MN1 were changed from Intellectual disability; dysmophic features; rhombencephalosynapsis to CEBALID syndrome, MIM#618774; Intellectual disability; dysmophic features; rhombencephalosynapsis
Mendeliome v0.2645 MN1 Zornitza Stark edited their review of gene: MN1: Changed phenotypes: CEBALID syndrome, MIM#618774, Intellectual disability, dysmophic features, rhombencephalosynapsis
Mendeliome v0.2645 PI4KA Zornitza Stark Gene: pi4ka has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2642 PI4KA Zornitza Stark Classified gene: PI4KA as Amber List (moderate evidence)
Mendeliome v0.2642 PI4KA Zornitza Stark Gene: pi4ka has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2641 PI4KA Zornitza Stark reviewed gene: PI4KA: Rating: AMBER; Mode of pathogenicity: None; Publications: 25855803; Phenotypes: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2637 VPS51 Zornitza Stark Gene: vps51 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2637 VPS51 Zornitza Stark Classified gene: VPS51 as Amber List (moderate evidence)
Mendeliome v0.2637 VPS51 Zornitza Stark Gene: vps51 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2636 VPS51 Zornitza Stark gene: VPS51 was added
gene: VPS51 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: VPS51 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS51 were set to 30624672; 31207318
Phenotypes for gene: VPS51 were set to Pontocerebellar hypoplasia, type 13, MIM# 618606
Review for gene: VPS51 was set to AMBER
Added comment: Two families reported with bi-allelic variants in this gene and global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable.
Sources: Expert list
Mendeliome v0.2627 RAMP2 Zornitza Stark Gene: ramp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2627 RAMP2 Zornitza Stark Classified gene: RAMP2 as Amber List (moderate evidence)
Mendeliome v0.2627 RAMP2 Zornitza Stark Gene: ramp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2626 RAMP2 Zornitza Stark gene: RAMP2 was added
gene: RAMP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAMP2 were set to 31000793
Phenotypes for gene: RAMP2 were set to Primary open angle glaucoma
Review for gene: RAMP2 was set to AMBER
Added comment: Six variants identified in 16 of 4763 POAG patients from large cohorts; none identified in 10,953 control individuals. Some functional data.
Sources: Literature
Mendeliome v0.2625 MEPE Zornitza Stark Classified gene: MEPE as Amber List (moderate evidence)
Mendeliome v0.2625 MEPE Zornitza Stark Gene: mepe has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2624 MEPE Zornitza Stark gene: MEPE was added
gene: MEPE was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MEPE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MEPE were set to 30287925
Phenotypes for gene: MEPE were set to hereditary congenital facial paresis; otosclerosis
Review for gene: MEPE was set to AMBER
Added comment: Single four-generation family reported with variant in this gene segregating nonprogressive HCFP and mixed hearing loss (HL). Damaging variants (truncating/frameshift) found to be enriched in otosclerosis cohort (p = 0.0006–0.0060).
Sources: Literature
Mendeliome v0.2621 POLR3GL Zornitza Stark Gene: polr3gl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2621 POLR3GL Zornitza Stark Classified gene: POLR3GL as Amber List (moderate evidence)
Mendeliome v0.2621 POLR3GL Zornitza Stark Gene: polr3gl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2620 POLR3GL Paul De Fazio gene: POLR3GL was added
gene: POLR3GL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POLR3GL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3GL were set to 31089205; 31695177
Phenotypes for gene: POLR3GL were set to endosteal hyperostosis; oligodontia; growth retardation; facial dysmorphisms; lipodystrophy
Review for gene: POLR3GL was set to AMBER
gene: POLR3GL was marked as current diagnostic
Added comment: Biallelic canonical splice variants were identified in monozygotic twins and another individual with similar phenotypes from 2 unrelated families. Variants were inherited from carrier parents. RNA studies confirmed exon skipping occurs in all affected individuals.

A separate study identified a homozygous nonsense variant in an individual with features of Neonatal progeroid syndrome/Wiedemann–Rautenstrauch syndrome. Quantitative PCR showed reduction in mRNA suggestive of NMD.
Sources: Literature
Mendeliome v0.2611 FOXF2 Zornitza Stark Gene: foxf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2611 FOXF2 Zornitza Stark Classified gene: FOXF2 as Amber List (moderate evidence)
Mendeliome v0.2611 FOXF2 Zornitza Stark Gene: foxf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2607 FOXF2 Hazel Phillimore changed review comment from: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639).
This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403).
Sources: Literature; to: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639).
This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403).
Previous names for FOXF2 include FKHL6 and FREAC2.
Sources: Literature
Mendeliome v0.2607 FOXF2 Hazel Phillimore gene: FOXF2 was added
gene: FOXF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOXF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOXF2 were set to PMID: 30561639; 22022403
Phenotypes for gene: FOXF2 were set to profound sensorineural hearing loss (SNHL); cochlea malformations; incomplete partition type I anomaly of the cochlea
Review for gene: FOXF2 was set to AMBER
Added comment: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639).
This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403).
Sources: Literature
Mendeliome v0.2600 LSR Zornitza Stark Gene: lsr has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2599 LSR Zornitza Stark Classified gene: LSR as Amber List (moderate evidence)
Mendeliome v0.2599 LSR Zornitza Stark Gene: lsr has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2598 LSR Zornitza Stark reviewed gene: LSR: Rating: AMBER; Mode of pathogenicity: None; Publications: 32303357, 30250217; Phenotypes: Cholestasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2597 LSR Zornitza Stark Classified gene: LSR as Amber List (moderate evidence)
Mendeliome v0.2597 LSR Zornitza Stark Gene: lsr has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2595 LSR Ee Ming Wong reviewed gene: LSR: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32303357, 30250217; Phenotypes: Intrahepatic cholestasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2584 ALPK1 Zornitza Stark Gene: alpk1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2584 ALPK1 Zornitza Stark Classified gene: ALPK1 as Amber List (moderate evidence)
Mendeliome v0.2584 ALPK1 Zornitza Stark Gene: alpk1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2583 ALPK1 Zornitza Stark gene: ALPK1 was added
gene: ALPK1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ALPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALPK1 were set to 31053777
Phenotypes for gene: ALPK1 were set to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome
Review for gene: ALPK1 was set to AMBER
Added comment: Three unrelated families reported. One of the variants segregated in four affected individuals in one family and another was found to be de novo. The third variant however was not segregated, and is also present in 18 individuals in gnomad. Hence the evidence for variant pathogenicity in this third case is not compelling.
Sources: Literature
Mendeliome v0.2582 LRRC32 Zornitza Stark Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2582 LRRC32 Zornitza Stark Classified gene: LRRC32 as Amber List (moderate evidence)
Mendeliome v0.2582 LRRC32 Zornitza Stark Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2581 LRRC32 Zornitza Stark gene: LRRC32 was added
gene: LRRC32 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LRRC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC32 were set to 30976112
Phenotypes for gene: LRRC32 were set to Intellectual disability; cleft palate; proliferative retinopathy
Review for gene: LRRC32 was set to AMBER
Added comment: Three individuals from two consanguineous families segregated the same homozygous bi-allelic variant, c.1630C>T; p.(Arg544Ter), shared haplotype indicative of founder effect. Mouse model has cleft palate and neonatal death.
Sources: Literature
Mendeliome v0.2580 KIF12 Ee Ming Wong gene: KIF12 was added
gene: KIF12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF12 were set to PMID: 30250217; 30976738
Phenotypes for gene: KIF12 were set to Prenatal cholestasis; High Gamma-Glutamyltransferase (GGT)
Review for gene: KIF12 was set to AMBER
gene: KIF12 was marked as current diagnostic
Added comment: > 3 unrelated families,but they are all consanguineous families
Sources: Literature
Mendeliome v0.2577 RHOA Zornitza Stark Phenotypes for gene: RHOA were changed from normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia to normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia; dental anomalies; body asymmetry; limb length discrepancy
Mendeliome v0.2575 RHOA Zornitza Stark reviewed gene: RHOA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31821646; Phenotypes: hypopigmented areas of the skin, dental anomalies, body asymmetry, limb length discrepancy, MRI abnormalities; Mode of inheritance: Other
Mendeliome v0.2572 RPSA Zornitza Stark changed review comment from: Four families reported with mono allelic variants and idiopathic intestinal varies.; to: Four families reported with mono allelic variants and idiopathic intestinal varies, often in combination with asplenia.
Mendeliome v0.2567 CRAT Zornitza Stark Gene: crat has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2567 CRAT Zornitza Stark Classified gene: CRAT as Amber List (moderate evidence)
Mendeliome v0.2567 CRAT Zornitza Stark Gene: crat has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2566 CRAT Zornitza Stark gene: CRAT was added
gene: CRAT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CRAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRAT were set to 29395073; 31448845
Phenotypes for gene: CRAT were set to Neurodegeneration with brain iron accumulation 8, MIM# 617917; Leigh syndrome
Review for gene: CRAT was set to AMBER
Added comment: Two unrelated families reported with bi-allelic variants, one with NBIA and one with Leigh syndrome phenotype.
Sources: Literature
Mendeliome v0.2561 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2558 B4GAT1 Zornitza Stark Classified gene: B4GAT1 as Amber List (moderate evidence)
Mendeliome v0.2558 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2557 B4GAT1 Zornitza Stark reviewed gene: B4GAT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23359570, 23877401; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 MIM# 615287; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2555 THG1L Zornitza Stark Classified gene: THG1L as Amber List (moderate evidence)
Mendeliome v0.2555 THG1L Zornitza Stark Gene: thg1l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2554 THG1L Zornitza Stark gene: THG1L was added
gene: THG1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: THG1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THG1L were set to 27307223; 31168944; 30214071
Phenotypes for gene: THG1L were set to Spinocerebellar ataxia, autosomal recessive 28, MIM# 618800
Review for gene: THG1L was set to AMBER
Added comment: Five individuals from two Ashkenazi Jewish families with same homozygous missense variant, and another family ascertained through a large microcephaly cohort, also with SCA.
Sources: Literature
Mendeliome v0.2547 C7orf43 Zornitza Stark Gene: c7orf43 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2547 C7orf43 Zornitza Stark Classified gene: C7orf43 as Amber List (moderate evidence)
Mendeliome v0.2547 C7orf43 Zornitza Stark Gene: c7orf43 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2546 C7orf43 Zornitza Stark gene: C7orf43 was added
gene: C7orf43 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C7orf43 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C7orf43 were set to 30715179
Phenotypes for gene: C7orf43 were set to Microcephaly 25, primary, autosomal recessive, MIM# 618351
Review for gene: C7orf43 was set to AMBER
Added comment: Single family reported: three affected siblings with homozygous truncating variant. Supportive zebrafish model.
Sources: Literature
Mendeliome v0.2530 SLC6A6 Zornitza Stark Gene: slc6a6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2493 C1orf194 Zornitza Stark Gene: c1orf194 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2492 C1orf194 Zornitza Stark Classified gene: C1orf194 as Amber List (moderate evidence)
Mendeliome v0.2492 C1orf194 Zornitza Stark Gene: c1orf194 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2490 UBA2 Zornitza Stark Gene: uba2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2490 UBA2 Zornitza Stark Classified gene: UBA2 as Amber List (moderate evidence)
Mendeliome v0.2490 UBA2 Zornitza Stark Gene: uba2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2475 SLC6A6 Zornitza Stark Classified gene: SLC6A6 as Amber List (moderate evidence)
Mendeliome v0.2475 SLC6A6 Zornitza Stark Gene: slc6a6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2474 MRPS14 Zornitza Stark Phenotypes for gene: MRPS14 were changed from Combined oxidative phosphorylation deficiency 38, MIM# 618378 to Combined oxidative phosphorylation deficiency 38, MIM# 618378; perinatal hypertrophic cardiomyopathy, growth retardation, muscle hypotonia, elevated lactate, dysmorphy and intellectual disability
Mendeliome v0.2471 ABCC1 Zornitza Stark Gene: abcc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2471 ABCC1 Zornitza Stark Classified gene: ABCC1 as Amber List (moderate evidence)
Mendeliome v0.2471 ABCC1 Zornitza Stark Gene: abcc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2470 ABCC1 Zornitza Stark gene: ABCC1 was added
gene: ABCC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ABCC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ABCC1 were set to 31273342
Phenotypes for gene: ABCC1 were set to Nonsyndromic hearing loss
Review for gene: ABCC1 was set to AMBER
Added comment: Total of 3 variants reported in 3 families, including 1 which segregates in a large family (10 affected) PMID: 31273342; Li 2019: Reported 3 different het missense in 3 families with postlingual ADNSHL. 1 missense segregated in a large Chinese family. This variant is present in gnomAD (10 hets), but onset noted to be in 2nd or 3rd decade of life. Functional studies performed. Other 2 variants reported absent in gnomAD. Amber rating in light of gnomad frequency of one of the reported variants.
Sources: Literature
Mendeliome v0.2460 GNAI2 Zornitza Stark Classified gene: GNAI2 as Amber List (moderate evidence)
Mendeliome v0.2460 GNAI2 Zornitza Stark Gene: gnai2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2459 GNAI2 Zornitza Stark reviewed gene: GNAI2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27787898; Phenotypes: Syndromic intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2455 FEM1B Zornitza Stark Gene: fem1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2454 FEM1B Zornitza Stark Classified gene: FEM1B as Amber List (moderate evidence)
Mendeliome v0.2454 FEM1B Zornitza Stark Gene: fem1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2452 SEC31A Zornitza Stark Gene: sec31a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2451 SEC31A Zornitza Stark Classified gene: SEC31A as Amber List (moderate evidence)
Mendeliome v0.2451 SEC31A Zornitza Stark Gene: sec31a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2449 SMCHD1 Zornitza Stark Added comment: Comment when marking as ready: Note association with FSHD2 is postulated to have digenic inheritance, caused by the combination of a heterozygous mutation in the SMCHD1 gene (614982) on chromosome 18p and presence of a haplotype on chromosome 4 that is permissive for DUX4 (606009) expression.
Mendeliome v0.2440 SLC6A6 Chern Lim gene: SLC6A6 was added
gene: SLC6A6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC6A6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC6A6 were set to 31345061; 31903486; 29886034
Phenotypes for gene: SLC6A6 were set to Early retinal degeneration; cardiomyopathy
Review for gene: SLC6A6 was set to AMBER
Added comment: Different homozygous missense variants in 2 unrelated consanguineous families with early retinal degeneration, some functional studies. Patients in one of the families also had cardiomyopathy. (PMIDs: 31345061, 31903486)

One dilated cardiomyopathy patient with a homozygous deletion at a splice site (PMID: 29886034).
Sources: Literature
Mendeliome v0.2440 MRPS14 Dean Phelan reviewed gene: MRPS14: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30358850; Phenotypes: perinatal hypertrophic cardiomyopathy, growth retardation, muscle hypotonia, elevated lactate, dysmorphy and intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2440 ORAI1 Natalie Tan changed review comment from: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence):
- Dominant ORAI1 missense variants via a GOF mechanism cause a spectrum of myopathy covering tubular aggregate myopathy/TAM and Stormorken syndrome/STRMK (slowly progressive muscle weakness with variable multisystemic disease including non-specific dysmorphism, a/hyposplenia, ichthyosis, cytopenias)
- Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy); to: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence):
- Dominant ORAI1 missense variants via a GOF mechanism cause a slowly progressive myopathy (tubular aggregate myopathy/TAM)
- Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy)
Mendeliome v0.2440 UBA2 Elena Savva gene: UBA2 was added
gene: UBA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UBA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: UBA2 were set to PMID: 31332306; 31587267
Phenotypes for gene: UBA2 were set to Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly
Penetrance for gene: UBA2 were set to unknown
Review for gene: UBA2 was set to AMBER
Added comment: No OMIM phenotype

PMID: 31332306 - a single patient with a de novo PTC and split hand/foot malformation (SHFM). Additional two multigenic CNVs including this gene in patients with SHFM and ectrodactyly. Authors mention an additional de novo missense but the patient didnt have SHFM, argue low penetrance

PMID: 31587267 - a mother and son with aplasia cutis congenita (ACC), with a heterozygous PTC. Son also has ectrodactyly. Authors note an additional de novo missense in a patient with ACC.
Sources: Literature
Mendeliome v0.2440 ORAI1 Natalie Tan changed review comment from: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence):
- Dominant ORAI1 missense variants via a GOF mechanism cause a spectrum of myopathy covering tubular aggregate myopathy/TAM and Stormorken syndrome/STRMK (slowly progressive muscle weakness with variable multisystemic disease including non-specific dysmorphism, a/hyposplenia, ichthyosis, cytopenias)
- Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy); to: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence):
- Dominant ORAI1 missense variants via a GOF mechanism cause a spectrum of myopathy covering tubular aggregate myopathy/TAM and Stormorken syndrome/STRMK (slowly progressive muscle weakness with variable multisystemic disease including non-specific dysmorphism, a/hyposplenia, ichthyosis, cytopenias)
- Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy)
Mendeliome v0.2440 GSX2 Zornitza Stark Gene: gsx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2440 REC114 Michelle Torres gene: REC114 was added
gene: REC114 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: REC114 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: REC114 were set to 30388401; 31704776
Phenotypes for gene: REC114 were set to Female infertility
Review for gene: REC114 was set to GREEN
Added comment: Three variants reported are either within or flanking exon 4.
- One hom patient (splice) had a miscarriage, 2 spontaneous complete hydatidiform moles, and 1 complete hydatidiform mole following intrauterine sperm injection (PMID: 30388401)
- Two hom unrelated patients from consanguineous families with abnormal pronuclear formation during fertilisation and subsequent early embrionic arrest resulting in female infertility. Both variants (1 missense and 1 splice) were shown to result in LoF (PMID: 31704776)
Sources: Literature
Mendeliome v0.2440 GSX2 Zornitza Stark Gene: gsx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2440 GSX2 Zornitza Stark Classified gene: GSX2 as Amber List (moderate evidence)
Mendeliome v0.2440 GSX2 Zornitza Stark Gene: gsx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2439 C1orf194 Ain Roesley gene: C1orf194 was added
gene: C1orf194 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C1orf194 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: C1orf194 were set to PMID: 31199454
Phenotypes for gene: C1orf194 were set to Charcot-Marie-Tooth
Review for gene: C1orf194 was set to AMBER
Added comment: PMID: 31199454; 2 missense variants in 2 large families segregating in an AD pattern. Mouse models for one of the variants (p.(Ile121Asn) led to impairments in moto and neuromuscular functions
Sources: Literature
Mendeliome v0.2439 POLR1B Paul De Fazio gene: POLR1B was added
gene: POLR1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POLR1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR1B were set to 31649276
Phenotypes for gene: POLR1B were set to bilateral malar and mandibular hypoplasia; microtia; coloboma; downslanting palpebral fissures; conductive deafness; cleft palate; heart malformations
Review for gene: POLR1B was set to AMBER
gene: POLR1B was marked as current diagnostic
Added comment: 6 individuals with Treacher-Collins syndrome described: 3 with de novo variants, one inherited from a mosaic father, and two inherited from affected mothers. Knockdown in zebrafish mimics the phenotype.
Sources: Literature
Mendeliome v0.2436 ACKR3 Zornitza Stark Gene: ackr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2435 ACKR3 Zornitza Stark Classified gene: ACKR3 as Amber List (moderate evidence)
Mendeliome v0.2435 ACKR3 Zornitza Stark Gene: ackr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2427 SLC9A7 Dean Phelan reviewed gene: SLC9A7: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30335141; Phenotypes: Intellectual disability; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.2416 ADAMTS19 Alison Yeung Gene: adamts19 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2416 ADAMTS19 Alison Yeung Classified gene: ADAMTS19 as Amber List (moderate evidence)
Mendeliome v0.2416 ADAMTS19 Alison Yeung Gene: adamts19 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2401 ADAMTS19 Crystle Lee edited their review of gene: ADAMTS19: Changed rating: AMBER
Mendeliome v0.2392 GNAI2 Elena Savva gene: GNAI2 was added
gene: GNAI2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GNAI2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GNAI2 were set to PMID: 31036916
Phenotypes for gene: GNAI2 were set to Pituitary adenoma, ACTH-secreting, somatic; Ventricular tachycardia, idiopathic 192605; Syndromic developmental disorder
Review for gene: GNAI2 was set to AMBER
Added comment: Papers associating this gene to tachycardia are very old (pre 2000, OMIM).

PMID: 31036916 - a single de novo patient with syndromic developmental disorder

Summary: AMBER - one report, may be a coincidental de novo finding
Sources: Literature
Mendeliome v0.2386 FEM1B Elena Savva gene: FEM1B was added
gene: FEM1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FEM1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FEM1B were set to PMID: 31036916
Phenotypes for gene: FEM1B were set to Syndromic global developmental delay
Review for gene: FEM1B was set to AMBER
Added comment: No OMIM phenotype

PMID: 31036916 - a single de novo patient reported in a neurodevelopmental disorder cohort. Authors note another de novo case with the exact same variant (p.Arg126Gln) from the DDD study, and a 3rd patient from GeneMatcher with the same de novo missense again. Decipher shows this variant to be in a highly constrained region of the protein.

Have selected AMBER for now - not sure if GeneMatcher findings can be used as a 3rd case
Sources: Literature
Mendeliome v0.2378 WIPI2 Melanie Marty gene: WIPI2 was added
gene: WIPI2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WIPI2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WIPI2 were set to 30968111
Phenotypes for gene: WIPI2 were set to Intellectual developmental disorder with short stature and variable skeletal anomalies 618453
Review for gene: WIPI2 was set to AMBER
Added comment: Four homozygous patients from one consanguineous family with intellectual developmental, short stature and variable skeletal anomalies. Functional studies in patient cells showed impaired protein function.
Sources: Literature
Mendeliome v0.2378 SEC31A Hazel Phillimore gene: SEC31A was added
gene: SEC31A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEC31A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEC31A were set to PMID: 30464055
Phenotypes for gene: SEC31A were set to congenital neurodevelopmental syndrome; spastic paraplegia; multiple contractures; profound developmental delay; epilepsy; failure to thrive
Review for gene: SEC31A was set to AMBER
Added comment: Frameshift. c.2776_2777, TA duplication, causing predicted p.A927fs*61 truncation and predicted NMD in 2 affected siblings in consanguineous Bedouin family with severe congenital neurological syndrome with spastic paraplegia, multiple contractures, profound developmental delay and convulsions. Failure to thrive. Lethal by age 4 years. Also had hearing defect, bilateral congenital cataract, horizontal nystagmus, with flat retina and optic atrophy. Supporting functional assays from knockout drosophila.
Sources: Literature
Mendeliome v0.2378 SLC44A1 Sebastian Lunke gene: SLC44A1 was added
gene: SLC44A1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC44A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC44A1 were set to 31855247
Phenotypes for gene: SLC44A1 were set to progressive ataxia; tremor; cognitive decline; dysphagia; optic atrophy; dysarthria
Review for gene: SLC44A1 was set to GREEN
Added comment: Four affected individuals from three families with homozygous frameshift variants. Functional evidence points to impaired choline transporter function yet unchanged membrane phosphatidylcholine content. Choline treatments may be beneficial.
Sources: Literature
Mendeliome v0.2376 PKDCC Alison Yeung Gene: pkdcc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2376 PKDCC Alison Yeung Classified gene: PKDCC as Amber List (moderate evidence)
Mendeliome v0.2376 PKDCC Alison Yeung Gene: pkdcc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2372 ACKR3 Elena Savva gene: ACKR3 was added
gene: ACKR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ACKR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACKR3 were set to PMID: 3121183
Phenotypes for gene: ACKR3 were set to Oculomotor synkinesis
Review for gene: ACKR3 was set to AMBER
Added comment: No phenotype currently listed in OMIM

PMID: 3121183 - 1 family (3 siblings and a cousin) with congenital ptosis and oculomotor synkinesis. Mouse model reciprocated the phenotype. Functional assay using transfected HEK293 cells show protein mislocalization and lower binding affinity

Emerging gene-disease association
Sources: Literature
Mendeliome v0.2365 ADAMTS19 Crystle Lee changed review comment from: PMID: 31844321; Wünnemann 2020: 4 affected in 2 unrelated consanguineous families with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Carriers unaffected. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype
Sources: Expert Review; to: Borderline amber/green
PMID: 31844321; Wünnemann 2020: 4 affected in 2 unrelated consanguineous families with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Carriers unaffected. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype
Sources: Expert Review
Mendeliome v0.2365 UBE3A Ain Roesley reviewed gene: UBE3A: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30842224; Phenotypes: Rett syndrome, Rett-like phenotypes; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2365 C9orf72 Elena Savva gene: C9orf72 was added
gene: C9orf72 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: C9orf72 were set to PMID: 30120348; 23284068
Phenotypes for gene: C9orf72 were set to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 105550
Review for gene: C9orf72 was set to AMBER
Added comment: Possibly RED

Caused by expansion of GGGGCC repeats, dont know if these qualify for mendeliome
Sources: Literature
Mendeliome v0.2365 ELOVL1 Hazel Phillimore reviewed gene: ELOVL1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30487246, 29496980; Phenotypes: ichthyosis, acanthosis nigricans, hypomyelination, spastic paraplegia, high frequency deafness, optic atrophy, nystagmus; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2364 CAP2 Melanie Marty gene: CAP2 was added
gene: CAP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CAP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAP2 were set to 30518548
Phenotypes for gene: CAP2 were set to Dilated cardiomyopathy
Review for gene: CAP2 was set to AMBER
Added comment: 2 patients with dilated cardiomyopathy from 1 consanguineous family. The splice variant identified in this family was proven to cause exon skipping and functional studies showed protein level was reduced. A Cap2 knockout mouse model correlated with the clinical phenotype of DCM and cardiac conduction disease, but not the other effects on growth, viability, wound healing and eye development.
Sources: Literature
Mendeliome v0.2361 PKDCC Paul De Fazio gene: PKDCC was added
gene: PKDCC was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PKDCC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PKDCC were set to PMID:30478137; 19097194
Phenotypes for gene: PKDCC were set to Dysmorphism; shortening of extremities
Review for gene: PKDCC was set to AMBER
gene: PKDCC was marked as current diagnostic
Added comment: 2 ("apparently") unrelated individuals with homozygous LoF (1x nonsense, 1x canonical splice) variants reported. Their phenotype is similar to knockout mice.
Sources: Literature
Mendeliome v0.2357 EMG1 Zornitza Stark Gene: emg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2357 EMG1 Zornitza Stark Classified gene: EMG1 as Amber List (moderate evidence)
Mendeliome v0.2357 EMG1 Zornitza Stark Gene: emg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2356 EMG1 Zornitza Stark gene: EMG1 was added
gene: EMG1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: EMG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EMG1 were set to 19463982
Phenotypes for gene: EMG1 were set to Bowen-Conradi syndrome, MIM#211180
Review for gene: EMG1 was set to AMBER
Added comment: Founder mutation in Hutterite, D86G.
Sources: Expert list
Mendeliome v0.2349 ATP2B4 Bryony Thompson Gene: atp2b4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2349 ATP2B4 Bryony Thompson Classified gene: ATP2B4 as Amber List (moderate evidence)
Mendeliome v0.2349 ATP2B4 Bryony Thompson Gene: atp2b4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2348 ATP2B4 Bryony Thompson gene: ATP2B4 was added
gene: ATP2B4 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ATP2B4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP2B4 were set to 25119969; 25798335; 29691679
Phenotypes for gene: ATP2B4 were set to Hereditary spastic paraplegia
Review for gene: ATP2B4 was set to AMBER
Added comment: One Chinese family segregating a missense variant with HSP and one HSP case with a assumed de novo nonsense variant. Supporting in vitro functional assays for the missense variant.
Sources: Expert list
Mendeliome v0.2339 DAG1 Zornitza Stark Phenotypes for gene: DAG1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, 613818; Walker-Warburg syndrome and tectocerebellar dysgraphia
Mendeliome v0.2310 CCT5 Bryony Thompson Classified gene: CCT5 as Amber List (moderate evidence)
Mendeliome v0.2310 CCT5 Bryony Thompson Gene: cct5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2309 CCT5 Bryony Thompson reviewed gene: CCT5: Rating: AMBER; Mode of pathogenicity: None; Publications: 16399879, 25124038, 25345891; Phenotypes: Neuropathy, hereditary sensory, with spastic paraplegia MIM#256840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2303 TRPC3 Bryony Thompson Gene: trpc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2303 TRPC3 Bryony Thompson Classified gene: TRPC3 as Amber List (moderate evidence)
Mendeliome v0.2303 TRPC3 Bryony Thompson Gene: trpc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2302 TRPC3 Bryony Thompson gene: TRPC3 was added
gene: TRPC3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TRPC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPC3 were set to 25477146; 19351902
Phenotypes for gene: TRPC3 were set to Spinocerebellar ataxia 41 MIM#616410
Mode of pathogenicity for gene: TRPC3 was set to Other
Review for gene: TRPC3 was set to AMBER
Added comment: A heterozygous gain-of function missense has been identified in a 40-year-old man with adult-onset spinocerebellar ataxia. A mouse model of dominant cerebellar ataxia, termed 'moonwalker', contains a gain-of-function variant in this gene.
Sources: Expert list
Mendeliome v0.2301 DAG1 Elena Savva reviewed gene: DAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29337005, 25503980; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, 613818, Walker-Warburg syndrome and tectocerebellar dysgraphia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2301 SLC9A1 Zornitza Stark Gene: slc9a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2301 SLC9A1 Zornitza Stark Classified gene: SLC9A1 as Amber List (moderate evidence)
Mendeliome v0.2301 SLC9A1 Zornitza Stark Gene: slc9a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2300 SLC9A1 Zornitza Stark gene: SLC9A1 was added
gene: SLC9A1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SLC9A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC9A1 were set to 25205112; 30018422; 25760855
Phenotypes for gene: SLC9A1 were set to Lichtenstein-Knorr syndrome, MIM# 616291
Review for gene: SLC9A1 was set to AMBER
Added comment: Two families with bi-allelic variants in this gene reported and combination of deafness and ataxia.
Sources: Expert list
Mendeliome v0.2299 MTCL1 Bryony Thompson Gene: mtcl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2299 MTCL1 Bryony Thompson Classified gene: MTCL1 as Amber List (moderate evidence)
Mendeliome v0.2299 MTCL1 Bryony Thompson Gene: mtcl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2298 MTCL1 Bryony Thompson gene: MTCL1 was added
gene: MTCL1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MTCL1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MTCL1 were set to 30548255; 28283581
Phenotypes for gene: MTCL1 were set to slowly progressive cerebellar ataxia; mild intellectual disability; seizures; episodic pain; spinocerebellar ataxia
Review for gene: MTCL1 was set to AMBER
Added comment: Single case with a homozygous loss of function variant in a Polish study of early-onset cerebellar ataxia, and a single family with a single heterozygous missense (p.Val1435Met) identified in two family members with adult-onset spinocerebellar ataxia. Mtcl1 gene disruption in mice results in abnormal motor coordination with Purkinje cell degeneration
Sources: Expert list
Mendeliome v0.2297 ATG5 Bryony Thompson Classified gene: ATG5 as Amber List (moderate evidence)
Mendeliome v0.2297 ATG5 Bryony Thompson Gene: atg5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2296 ATG5 Bryony Thompson gene: ATG5 was added
gene: ATG5 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ATG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG5 were set to 16625204; 26812546
Phenotypes for gene: ATG5 were set to Spinocerebellar ataxia, autosomal recessive 25 MIM#617584
Review for gene: ATG5 was set to AMBER
Added comment: A homozgyous variant was identified in a single family with two affected siblings. Mice deficient for Atg5 specifically in neural cells and Atg5 null Drosophila develop progressive deficits in motor function.
Sources: Expert list
Mendeliome v0.2290 ACOX2 Zornitza Stark Gene: acox2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2290 ACOX2 Zornitza Stark Classified gene: ACOX2 as Amber List (moderate evidence)
Mendeliome v0.2290 ACOX2 Zornitza Stark Gene: acox2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2289 ACOX2 Zornitza Stark gene: ACOX2 was added
gene: ACOX2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ACOX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACOX2 were set to 27647924; 27884763
Phenotypes for gene: ACOX2 were set to Bile acid synthesis defect, congenital, 6, 617308
Review for gene: ACOX2 was set to AMBER
Added comment: Two unrelated families reported.
Sources: Expert Review
Mendeliome v0.2282 SIPA1L3 Bryony Thompson Gene: sipa1l3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2282 SIPA1L3 Bryony Thompson Classified gene: SIPA1L3 as Amber List (moderate evidence)
Mendeliome v0.2282 SIPA1L3 Bryony Thompson Gene: sipa1l3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2281 SIPA1L3 Bryony Thompson gene: SIPA1L3 was added
gene: SIPA1L3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SIPA1L3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SIPA1L3 were set to 28951961; 27993984; 25804400
Phenotypes for gene: SIPA1L3 were set to Cataract 45 MIM#616851
Review for gene: SIPA1L3 was set to AMBER
Added comment: A consanguineous German family segregating a homozygous nonsense mutation in two sisters with congenital cataracts (PMID: 25804400). Null Zebrafish, Xenopus and mouse models recapitulate the human cataract phenotype. A case with congenital cataracts as a feature of their condition harboured a de novo balanced chromosomal translocation, 46,XY,t(2;19)(q37.3;q13.1), where breakpoint mapping and sequencing showed a physical disruption of the 5′UTR of SIPA1L3 (PMID: 26231217). In a case with bilateral congenital cataracts a heterozygous missense (D148Y) was identified and in vitro functional assays of the variant resulted in abnormal actin morphology (PMID: 26231217).
Sources: Expert list
Mendeliome v0.2262 MARS2 Zornitza Stark Phenotypes for gene: MARS2 were changed from to Combined oxidative phosphorylation deficiency 25, OMIM #616430; Spastic ataxia 3, autosomal recessive, OMIM #611390
Mendeliome v0.2259 MARS2 Zornitza Stark changed review comment from: 1 family with 2 sibs with combined oxidative phosphorylation deficiency-25 (with ID) with compound heterozygous mutations in the MARS2 gene. Patient fibroblasts showed decreased activities of mitochondrial complexes I and IV, consistent with a mitochondrial translation defect. Immunoblot analysis showed reduced MARS2 protein levels as well as reduced levels of selected subunits of complexes I and IV.; to: 1 family with 2 sibs with combined oxidative phosphorylation deficiency-25 (with ID) with compound heterozygous mutations in the MARS2 gene. Patient fibroblasts showed decreased activities of mitochondrial complexes I and IV, consistent with a mitochondrial translation defect. Immunoblot analysis showed reduced MARS2 protein levels as well as reduced levels of selected subunits of complexes I and IV. Spastic ataxia association: note complex chromosomal rearrangements rather than SNVs reported in group of 54 French Canadians.
Mendeliome v0.2259 MECOM Zornitza Stark Phenotypes for gene: MECOM were changed from to Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, MIM#616738
Mendeliome v0.2239 ANLN Zornitza Stark Gene: anln has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2213 ADAM22 Zornitza Stark Gene: adam22 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2213 ADAM22 Zornitza Stark Classified gene: ADAM22 as Amber List (moderate evidence)
Mendeliome v0.2213 ADAM22 Zornitza Stark Gene: adam22 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2212 HOXB6 Zornitza Stark Classified gene: HOXB6 as Amber List (moderate evidence)
Mendeliome v0.2212 HOXB6 Zornitza Stark Gene: hoxb6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2211 QRSL1 Zornitza Stark Phenotypes for gene: QRSL1 were changed from to Combined oxidative phosphorylation deficiency 40
Mendeliome v0.2208 QRSL1 Zornitza Stark reviewed gene: QRSL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26741492, 29440775, 30283131, 30642647; Phenotypes: Combined oxidative phosphorylation deficiency 40; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2208 PPCS Zornitza Stark Gene: ppcs has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2205 PPCS Zornitza Stark Classified gene: PPCS as Amber List (moderate evidence)
Mendeliome v0.2205 PPCS Zornitza Stark Gene: ppcs has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2204 PPCS Zornitza Stark reviewed gene: PPCS: Rating: AMBER; Mode of pathogenicity: None; Publications: 29754768; Phenotypes: Cardiomyopathy, dilated, 2C, MIM# 618189; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2204 PET117 Zornitza Stark gene: PET117 was added
gene: PET117 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PET117 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PET117 were set to 28386624
Phenotypes for gene: PET117 were set to Developmental delay; Regression; Complex IV deficiency
Review for gene: PET117 was set to RED
Added comment: Two siblings reported, some functional data. PET117 postulated to be a Complex IV assembly factor.
Sources: Expert list
Mendeliome v0.2200 TMTC2 Zornitza Stark Gene: tmtc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2194 TMTC2 Zornitza Stark Classified gene: TMTC2 as Amber List (moderate evidence)
Mendeliome v0.2194 TMTC2 Zornitza Stark Gene: tmtc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2181 CLIC5 Zornitza Stark Gene: clic5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2181 GNB2 Zornitza Stark Gene: gnb2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2181 MIR96 Zornitza Stark Gene: mir96 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2181 MYL1 Zornitza Stark Gene: myl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2180 TFAM Zornitza Stark Gene: tfam has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2180 TFAM Zornitza Stark Classified gene: TFAM as Amber List (moderate evidence)
Mendeliome v0.2180 TFAM Zornitza Stark Gene: tfam has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2179 NME3 Zornitza Stark gene: NME3 was added
gene: NME3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NME3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NME3 were set to 30587587
Phenotypes for gene: NME3 were set to Hypotonia; Neurodegeneration; Abnormal mitochondrial dynamics
Review for gene: NME3 was set to RED
Added comment: Single individual reported. NME3 is a mitochondrial outer-membrane protein capable of interacting with MFN1/2, and its depletion causes dysfunction in mitochondrial dynamics
Sources: Expert list
Mendeliome v0.2176 MRPS23 Zornitza Stark Phenotypes for gene: MRPS23 were changed from Hepatic disease; Combined respiratory chain complex deficiencies to Hepatic disease; Combined respiratory chain complex deficienciesHepatic disease; Combined respiratory chain complex deficiencies; Cardiomyopathy; Tubulopathy; Lactic acidosis; Structural brain abnormalities
Mendeliome v0.2173 MRPS23 Zornitza Stark edited their review of gene: MRPS23: Added comment: Four families reported.; Changed rating: GREEN; Changed publications: 26741492, 17873122, 25663021, 28752220; Changed phenotypes: Hepatic disease, Combined respiratory chain complex deficiencies, Cardiomyopathy, Tubulopathy, Lactic acidosis, Structural brain abnormalities
Mendeliome v0.2172 ERAL1 Zornitza Stark Gene: eral1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2172 ERAL1 Zornitza Stark Classified gene: ERAL1 as Amber List (moderate evidence)
Mendeliome v0.2172 ERAL1 Zornitza Stark Gene: eral1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2171 ERAL1 Zornitza Stark gene: ERAL1 was added
gene: ERAL1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ERAL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERAL1 were set to 28449065
Phenotypes for gene: ERAL1 were set to Perrault syndrome 6, MIM# 617565
Review for gene: ERAL1 was set to AMBER
Added comment: Three individuals from same small geographical location with homozygous missense variant in this gene, functional data.
Sources: Expert list
Mendeliome v0.2169 TRAF3IP2 Zornitza Stark Gene: traf3ip2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2166 TRAF3IP2 Zornitza Stark Classified gene: TRAF3IP2 as Amber List (moderate evidence)
Mendeliome v0.2166 TRAF3IP2 Zornitza Stark Gene: traf3ip2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2165 TRAF3IP2 Zornitza Stark reviewed gene: TRAF3IP2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24120361, 31292894, 20660351; Phenotypes: Candidiasis, familial, 8, MIM# 615527; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2153 TNFRSF13C Zornitza Stark Gene: tnfrsf13c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2150 TNFRSF13C Zornitza Stark Classified gene: TNFRSF13C as Amber List (moderate evidence)
Mendeliome v0.2150 TNFRSF13C Zornitza Stark Gene: tnfrsf13c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2149 TNFRSF13C Zornitza Stark reviewed gene: TNFRSF13C: Rating: AMBER; Mode of pathogenicity: None; Publications: 19666484, 26613719; Phenotypes: Immunodeficiency, common variable, 4, MIM# 613494; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2146 THBD Zornitza Stark Gene: thbd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2143 THBD Zornitza Stark Classified gene: THBD as Amber List (moderate evidence)
Mendeliome v0.2143 THBD Zornitza Stark Gene: thbd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2142 THBD Zornitza Stark reviewed gene: THBD: Rating: AMBER; Mode of pathogenicity: None; Publications: 29500241, 19625716; Phenotypes: {Hemolytic uremic syndrome, atypical, susceptibility to, 6}, MIM# 612926; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2135 SEMA3E Zornitza Stark Gene: sema3e has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2133 SEMA3E Zornitza Stark Classified gene: SEMA3E as Amber List (moderate evidence)
Mendeliome v0.2133 SEMA3E Zornitza Stark Gene: sema3e has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2132 SEMA3E Zornitza Stark reviewed gene: SEMA3E: Rating: AMBER; Mode of pathogenicity: None; Publications: 15235037, 31691538, 31464029; Phenotypes: CHARGE syndrome, MIM#214800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2132 RNF31 Zornitza Stark Gene: rnf31 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2129 RNF31 Zornitza Stark Classified gene: RNF31 as Amber List (moderate evidence)
Mendeliome v0.2129 RNF31 Zornitza Stark Gene: rnf31 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2128 RNF31 Zornitza Stark reviewed gene: RNF31: Rating: AMBER; Mode of pathogenicity: None; Publications: 26008899, 30936877; Phenotypes: Immune deficiency, Autoinflammation; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2124 PSMB9 Zornitza Stark Marked gene: PSMB9 as ready
Mendeliome v0.2124 PSMB9 Zornitza Stark Gene: psmb9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2124 PSMB9 Zornitza Stark Phenotypes for gene: PSMB9 were changed from to Proteasome-associated autoinflammatory syndrome 3, digenic, MIM# 617591
Mendeliome v0.2123 PSMB9 Zornitza Stark Publications for gene: PSMB9 were set to
Mendeliome v0.2122 PSMB9 Zornitza Stark Mode of inheritance for gene: PSMB9 was changed from Unknown to Other
Mendeliome v0.2121 PSMB9 Zornitza Stark Classified gene: PSMB9 as Amber List (moderate evidence)
Mendeliome v0.2121 PSMB9 Zornitza Stark Gene: psmb9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2120 PSMB9 Zornitza Stark reviewed gene: PSMB9: Rating: AMBER; Mode of pathogenicity: None; Publications: 26524591; Phenotypes: Proteasome-associated autoinflammatory syndrome 3, digenic, MIM# 617591; Mode of inheritance: Other
Mendeliome v0.2120 PSMB4 Zornitza Stark Marked gene: PSMB4 as ready
Mendeliome v0.2120 PSMB4 Zornitza Stark Gene: psmb4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2120 PSMB4 Zornitza Stark Phenotypes for gene: PSMB4 were changed from to Proteasome-associated autoinflammatory syndrome 3 and digenic forms, MIM# 617591
Mendeliome v0.2119 PSMB4 Zornitza Stark Publications for gene: PSMB4 were set to
Mendeliome v0.2118 PSMB4 Zornitza Stark Mode of inheritance for gene: PSMB4 was changed from Unknown to Other
Mendeliome v0.2117 PSMB4 Zornitza Stark Classified gene: PSMB4 as Amber List (moderate evidence)
Mendeliome v0.2117 PSMB4 Zornitza Stark Gene: psmb4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2116 PSMB4 Zornitza Stark reviewed gene: PSMB4: Rating: AMBER; Mode of pathogenicity: None; Publications: 26524591; Phenotypes: Proteasome-associated autoinflammatory syndrome 3 and digenic forms, MIM# 617591; Mode of inheritance: Other
Mendeliome v0.2116 PSMA3 Zornitza Stark Gene: psma3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2113 PSMA3 Zornitza Stark Classified gene: PSMA3 as Amber List (moderate evidence)
Mendeliome v0.2113 PSMA3 Zornitza Stark Gene: psma3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2112 PSMA3 Zornitza Stark reviewed gene: PSMA3: Rating: AMBER; Mode of pathogenicity: None; Publications: 26524591; Phenotypes: Proteasome-associated autoinflammatory syndrome 1 and digenic forms, MIM#256040; Mode of inheritance: Other
Mendeliome v0.2098 IRF7 Zornitza Stark Gene: irf7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2095 IRF7 Zornitza Stark Classified gene: IRF7 as Amber List (moderate evidence)
Mendeliome v0.2095 IRF7 Zornitza Stark Gene: irf7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2094 IRF7 Zornitza Stark reviewed gene: IRF7: Rating: AMBER; Mode of pathogenicity: None; Publications: 25814066, 15800576; Phenotypes: Immunodeficiency 39, MIM# 616345; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2083 FCN3 Zornitza Stark Gene: fcn3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2080 FCN3 Zornitza Stark Classified gene: FCN3 as Amber List (moderate evidence)
Mendeliome v0.2080 FCN3 Zornitza Stark Gene: fcn3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2079 FCN3 Zornitza Stark reviewed gene: FCN3: Rating: AMBER; Mode of pathogenicity: None; Publications: 25662573, 22226667, 19535802, 20971976; Phenotypes: Immunodeficiency due to ficolin 3 deficiency, MIM# 613860; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2079 FCGR3A Zornitza Stark Gene: fcgr3a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2076 FCGR3A Zornitza Stark Classified gene: FCGR3A as Amber List (moderate evidence)
Mendeliome v0.2076 FCGR3A Zornitza Stark Gene: fcgr3a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2075 FCGR3A Zornitza Stark reviewed gene: FCGR3A: Rating: AMBER; Mode of pathogenicity: None; Publications: 8874200, 23006327, 8608639; Phenotypes: Immunodeficiency 20, MIM# 615707; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2075 CR2 Zornitza Stark Gene: cr2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2072 CR2 Zornitza Stark Classified gene: CR2 as Amber List (moderate evidence)
Mendeliome v0.2072 CR2 Zornitza Stark Gene: cr2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2071 CR2 Zornitza Stark reviewed gene: CR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 22035880, 26325596; Phenotypes: Immunodeficiency, common variable, 7, MIM# 614699; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2063 CFB Zornitza Stark Gene: cfb has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2060 CFB Zornitza Stark Classified gene: CFB as Amber List (moderate evidence)
Mendeliome v0.2060 CFB Zornitza Stark Gene: cfb has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2059 CFB Zornitza Stark reviewed gene: CFB: Rating: AMBER; Mode of pathogenicity: None; Publications: 24152280; Phenotypes: Complement factor B deficiency, MIM# 615561; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2059 CD8A Zornitza Stark Gene: cd8a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2056 CD8A Zornitza Stark Classified gene: CD8A as Amber List (moderate evidence)
Mendeliome v0.2056 CD8A Zornitza Stark Gene: cd8a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2055 CD8A Zornitza Stark reviewed gene: CD8A: Rating: AMBER; Mode of pathogenicity: None; Publications: 11435463, 17658607, 26563160; Phenotypes: CD8 deficiency, familial, MIM# 608957; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2055 CD81 Zornitza Stark Gene: cd81 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2052 CD81 Zornitza Stark Classified gene: CD81 as Amber List (moderate evidence)
Mendeliome v0.2052 CD81 Zornitza Stark Gene: cd81 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2051 CD81 Zornitza Stark reviewed gene: CD81: Rating: AMBER; Mode of pathogenicity: None; Publications: 20237408; Phenotypes: Immunodeficiency, common variable, 6, MIM# 613496; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2050 CD247 Zornitza Stark changed review comment from: Also known as CD3Z. Single individual reported with homozygous germline nonsense variant, which was present in some T cells, but others had the nonsense variant in combination with one of three different missense somatic variants.; to: Also known as CD3Z. Note one individual reported with homozygous germline nonsense variant, which was present in some T cells, but others had the nonsense variant in combination with one of three different missense somatic variants.
Mendeliome v0.2049 BLOC1S6 Zornitza Stark Gene: bloc1s6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2046 BLOC1S6 Zornitza Stark Classified gene: BLOC1S6 as Amber List (moderate evidence)
Mendeliome v0.2046 BLOC1S6 Zornitza Stark Gene: bloc1s6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2045 BLOC1S6 Zornitza Stark reviewed gene: BLOC1S6: Rating: AMBER; Mode of pathogenicity: None; Publications: 22461475, 21665000, 32245340; Phenotypes: Hermansky-Pudlak syndrome 9, MIM# 614171; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2039 AP1S3 Zornitza Stark Gene: ap1s3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2036 AP1S3 Zornitza Stark Classified gene: AP1S3 as Amber List (moderate evidence)
Mendeliome v0.2036 AP1S3 Zornitza Stark Gene: ap1s3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2035 AP1S3 Zornitza Stark reviewed gene: AP1S3: Rating: AMBER; Mode of pathogenicity: None; Publications: 24791904, 27388993; Phenotypes: {Psoriasis 15, pustular, susceptibility to} 616106; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2020 ICOSLG Zornitza Stark Gene: icoslg has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2020 ICOSLG Zornitza Stark Phenotypes for gene: ICOSLG were changed from to Combined immunodeficiency; recurrent bacterial and viral infections; neutropaenia
Mendeliome v0.2017 ICOSLG Zornitza Stark Classified gene: ICOSLG as Amber List (moderate evidence)
Mendeliome v0.2017 ICOSLG Zornitza Stark Gene: icoslg has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2016 ICOSLG Zornitza Stark reviewed gene: ICOSLG: Rating: AMBER; Mode of pathogenicity: None; Publications: 31532372, 30498080; Phenotypes: Combined immunodeficiency, recurrent bacterial and viral infections, neutropaenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2016 IL6ST Zornitza Stark Phenotypes for gene: IL6ST were changed from Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response. to Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response; Hyper-IgE syndrome, autosomal dominant
Mendeliome v0.2013 IL6ST Zornitza Stark changed review comment from: Also known as gp130. Two families with bi-allelic missense variants and immunological phenotype described initially. More recently, five individuals from three families reported with a more complex Stuve-Wiedemann-like phenotype reported, including skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. These three families had bi-allelic LoF variants (nonsense and canonical splice site). Several mouse models support gene-disease association.
Sources: Expert list; to: Also known as gp130. Two families with bi-allelic missense variants and immunological phenotype described initially. More recently, five individuals from three families reported with a more complex Stuve-Wiedemann-like phenotype reported, including skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. These three families had bi-allelic LoF variants (nonsense and canonical splice site). Several mouse models support gene-disease association.
2020: 12 individuals from 8 unrelated families with seven different mono-allelic truncating variants, dominant negative effect proposed.
Sources: Expert list
Mendeliome v0.2013 IL6ST Zornitza Stark edited their review of gene: IL6ST: Changed publications: 28747427, 30309848, 12370259, 16041381, 31914175, 32207811; Changed phenotypes: Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523, Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response, Hyper-IgE syndrome, autosomal dominant; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2004 UBE2T Zornitza Stark Gene: ube2t has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2001 UBE2T Zornitza Stark Classified gene: UBE2T as Amber List (moderate evidence)
Mendeliome v0.2001 UBE2T Zornitza Stark Gene: ube2t has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2000 UBE2T Zornitza Stark reviewed gene: UBE2T: Rating: AMBER; Mode of pathogenicity: None; Publications: 26046368; Phenotypes: Fanconi anemia, complementation group T, MIM# 616435; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1996 ALPI Zornitza Stark Gene: alpi has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1996 ALPI Zornitza Stark Classified gene: ALPI as Amber List (moderate evidence)
Mendeliome v0.1996 ALPI Zornitza Stark Gene: alpi has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1995 ALPI Zornitza Stark gene: ALPI was added
gene: ALPI was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ALPI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALPI were set to 29567797
Phenotypes for gene: ALPI were set to Inflammatory bowel disease
Review for gene: ALPI was set to AMBER
Added comment: Two unrelated individuals, some functional data.
Sources: Expert list
Mendeliome v0.1987 HMOX1 Zornitza Stark reviewed gene: HMOX1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21088618, 9884342, 20844238; Phenotypes: Heme oxygenase-1 deficiency, MIM# 614034, Asplenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1983 POLR3C Zornitza Stark Gene: polr3c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1983 POLR3C Zornitza Stark Classified gene: POLR3C as Amber List (moderate evidence)
Mendeliome v0.1983 POLR3C Zornitza Stark Gene: polr3c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1982 POLR3C Zornitza Stark gene: POLR3C was added
gene: POLR3C was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: POLR3C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR3C were set to 28783042
Phenotypes for gene: POLR3C were set to Severe VZV infection
Review for gene: POLR3C was set to AMBER
Added comment: One individual with POLR3C variant and another individual with both POL3RA and POL3RC variants.
Sources: Expert list
Mendeliome v0.1975 IFNAR1 Zornitza Stark Gene: ifnar1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1975 IFNAR1 Zornitza Stark Classified gene: IFNAR1 as Amber List (moderate evidence)
Mendeliome v0.1975 IFNAR1 Zornitza Stark Gene: ifnar1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1974 IFNAR1 Zornitza Stark gene: IFNAR1 was added
gene: IFNAR1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IFNAR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFNAR1 were set to 31270247
Phenotypes for gene: IFNAR1 were set to Severe disease caused by Yellow Fever vaccine and Measles vaccine
Review for gene: IFNAR1 was set to AMBER
Added comment: Two unrelated individuals reported with bi-allelic LoF variants, some functional data.
Sources: Expert list
Mendeliome v0.1973 IRF9 Zornitza Stark Gene: irf9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1973 IRF9 Zornitza Stark Classified gene: IRF9 as Amber List (moderate evidence)
Mendeliome v0.1973 IRF9 Zornitza Stark Gene: irf9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1972 IRF9 Zornitza Stark gene: IRF9 was added
gene: IRF9 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IRF9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IRF9 were set to 30826365; 30143481
Phenotypes for gene: IRF9 were set to Immunodeficiency 65, susceptibility to viral infections 618648
Review for gene: IRF9 was set to AMBER
Added comment: Two families reported.
Sources: Expert list
Mendeliome v0.1966 JAK1 Zornitza Stark Classified gene: JAK1 as Amber List (moderate evidence)
Mendeliome v0.1966 JAK1 Zornitza Stark Gene: jak1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1965 JAK1 Zornitza Stark edited their review of gene: JAK1: Changed rating: AMBER; Changed publications: 28111307, 28008925, 30671064; Changed phenotypes: Eosinophilia, Eosinophilic enteritis, Thyroid disease, Poor growth, Viral infections, Susceptibility to mycobacteria and viruses; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1965 SPPL2A Zornitza Stark Gene: sppl2a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1965 SPPL2A Zornitza Stark Classified gene: SPPL2A as Amber List (moderate evidence)
Mendeliome v0.1965 SPPL2A Zornitza Stark Gene: sppl2a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1964 SPPL2A Zornitza Stark gene: SPPL2A was added
gene: SPPL2A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SPPL2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPPL2A were set to 30127434
Phenotypes for gene: SPPL2A were set to Susceptibility to mycobacteria and Salmonella
Review for gene: SPPL2A was set to AMBER
Added comment: Three individuals from two unrelated consanguineous family with two different homozygous splice site variants, functional data.
Sources: Expert list
Mendeliome v0.1956 MKL1 Zornitza Stark Gene: mkl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1956 MKL1 Zornitza Stark Classified gene: MKL1 as Amber List (moderate evidence)
Mendeliome v0.1956 MKL1 Zornitza Stark Gene: mkl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1955 MKL1 Zornitza Stark gene: MKL1 was added
gene: MKL1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MKL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MKL1 were set to 32128589; 26224645
Phenotypes for gene: MKL1 were set to Neutropaenia with combined immune deficiency
Review for gene: MKL1 was set to AMBER
Added comment: Two unrelated families reported.
Sources: Expert list
Mendeliome v0.1935 TOP2B Zornitza Stark Phenotypes for gene: TOP2B were changed from Autosomal dominant deafness to Autosomal dominant deafness; Antibody deficiency, recurrent infections, facial dysmorphism, limb anomalies; Intellectual disability
Mendeliome v0.1933 TOP2B Zornitza Stark edited their review of gene: TOP2B: Changed publications: 28343847, 31198993, 31409799, 12773624; Changed phenotypes: Autosomal dominant deafness, Antibody deficiency, recurrent infections, facial dysmorphism, limb anomalies, Intellectual disability
Mendeliome v0.1932 TOP2B Zornitza Stark edited their review of gene: TOP2B: Changed rating: GREEN; Changed publications: 31198993, 31409799, 31953910; Changed phenotypes: Autosomal dominant deafness, Antibody deficiency, recurrent infections, facial dysmorphism, limb anomalies
Mendeliome v0.1931 SLC39A7 Zornitza Stark gene: SLC39A7 was added
gene: SLC39A7 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SLC39A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A7 were set to 30718914
Phenotypes for gene: SLC39A7 were set to Antibody deficiency; early onset infections; blistering dermatosis; failure to thrive; thrombocytopaenia
Review for gene: SLC39A7 was set to GREEN
Added comment: Five unrelated families with hypomorphic variants and a mouse model recapitulating phenotype.
Sources: Expert list
Mendeliome v0.1928 ERBIN Zornitza Stark Gene: erbin has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1928 ERBIN Zornitza Stark Classified gene: ERBIN as Amber List (moderate evidence)
Mendeliome v0.1928 ERBIN Zornitza Stark Gene: erbin has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1927 ERBIN Zornitza Stark gene: ERBIN was added
gene: ERBIN was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ERBIN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ERBIN were set to 28126831
Phenotypes for gene: ERBIN were set to Recurrent respiratory infections; Susceptibility to S.aureus; Eczema; Hyperextensible joints; Scoliosis; Arterial dilatation in some
Review for gene: ERBIN was set to AMBER
Added comment: Single family and functional data.
Sources: Expert list
Mendeliome v0.1923 IL6ST Zornitza Stark gene: IL6ST was added
gene: IL6ST was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IL6ST was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL6ST were set to 28747427; 30309848; 12370259; 16041381; 31914175
Phenotypes for gene: IL6ST were set to Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response.
Review for gene: IL6ST was set to GREEN
Added comment: Also known as gp130. Two families with bi-allelic missense variants and immunological phenotype described initially. More recently, five individuals from three families reported with a more complex Stuve-Wiedemann-like phenotype reported, including skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. These three families had bi-allelic LoF variants (nonsense and canonical splice site). Several mouse models support gene-disease association.
Sources: Expert list
Mendeliome v0.1922 IL6R Zornitza Stark Gene: il6r has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1919 IL6R Zornitza Stark Classified gene: IL6R as Amber List (moderate evidence)
Mendeliome v0.1919 IL6R Zornitza Stark Gene: il6r has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1918 IL6R Zornitza Stark reviewed gene: IL6R: Rating: AMBER; Mode of pathogenicity: None; Publications: 31235509; Phenotypes: Recurrent pyogenic infections, cold abscesses, High circulating IL-6 levels, High IgE; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1918 NSMCE2 Zornitza Stark Gene: nsmce2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1917 LIG1 Zornitza Stark gene: LIG1 was added
gene: LIG1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: LIG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIG1 were set to 30395541
Phenotypes for gene: LIG1 were set to Combined immunodeficiency; Lymphopaenia; Hypogammaglobulinaemia; Recurrent bacterial and viral infections; Growth retardation; Sun sensitivity, radiation sensitivity; Macrocytosis
Review for gene: LIG1 was set to GREEN
Added comment: Five individuals from three families.
Sources: Expert list
Mendeliome v0.1916 POLE2 Zornitza Stark gene: POLE2 was added
gene: POLE2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: POLE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLE2 were set to 26365386
Phenotypes for gene: POLE2 were set to Combined immunodeficiency; Lymphopaenia; Lack of TRECS, absent proliferation in response to antigens; Hypoglobulinaemia; Recurrent infections, disseminated BCG infections; Autoimmunity; Facial dysmorphism
Review for gene: POLE2 was set to RED
Added comment: Single family reported with homozygous splice site variant.
Sources: Expert list
Mendeliome v0.1914 FCHO1 Zornitza Stark gene: FCHO1 was added
gene: FCHO1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FCHO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FCHO1 were set to 32098969; 30822429
Phenotypes for gene: FCHO1 were set to Combined immunodeficiency; T cells: low, poor proliferation; B cells: normal number; Recurrent infections (viral, mycobacteria, bacterial, fungal); lymphoproliferation; Failure to thrive; Increased activation-induced T-cell death; Defective clathrin-mediated endocytosis
Review for gene: FCHO1 was set to GREEN
Added comment: More than 10 affected individuals with bi-allelic variants in this gene reported. Functional data.
Sources: Expert list
Mendeliome v0.1913 REL Zornitza Stark gene: REL was added
gene: REL was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: REL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: REL were set to 31103457
Phenotypes for gene: REL were set to Combined immunodeficiency; T cells: normal, decreased memory CD4, poor proliferation; B cells: low, mostly naive, few switched memory B cells, impaired proliferation; Recurrent infections with bacteria, mycobacteria, salmonella and opportunistic organisms; Defective innate immunity
Review for gene: REL was set to RED
Added comment: Single individual from consanguineous family reported with homozygous canonical splice site variant, no functional data.
Sources: Expert list
Mendeliome v0.1912 TFRC Zornitza Stark Gene: tfrc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1912 TFRC Zornitza Stark Phenotypes for gene: TFRC were changed from to Immunodeficiency 46, MIM# 616740; T cells: normal number, poor proliferation; B cells: normal number, low memory B cells; recurrent infections, neutorpaenia; thrombocytopaenia
Mendeliome v0.1909 TFRC Zornitza Stark Classified gene: TFRC as Amber List (moderate evidence)
Mendeliome v0.1909 TFRC Zornitza Stark Gene: tfrc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1908 TFRC Zornitza Stark reviewed gene: TFRC: Rating: AMBER; Mode of pathogenicity: None; Publications: 26642240; Phenotypes: Immunodeficiency 46, MIM# 616740, T cells: normal number, poor proliferation, B cells: normal number, low memory B cells, recurrent infections, neutorpaenia, thrombocytopaenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1908 RELA Zornitza Stark Gene: rela has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1908 RELA Zornitza Stark Classified gene: RELA as Amber List (moderate evidence)
Mendeliome v0.1908 RELA Zornitza Stark Gene: rela has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1907 RELA Zornitza Stark gene: RELA was added
gene: RELA was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RELA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RELA were set to 28600438; 29305315
Phenotypes for gene: RELA were set to Mucocutaneous ulceration, chronic, MIM# 618287; Impaired NFkB activation; reduced production of inflammatory cytokines; autoimmune cytopaenias
Review for gene: RELA was set to AMBER
Added comment: Two families reported, somewhat different phenotypes.
Sources: Expert list
Mendeliome v0.1906 RELB Zornitza Stark Gene: relb has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1906 RELB Zornitza Stark Classified gene: RELB as Amber List (moderate evidence)
Mendeliome v0.1906 RELB Zornitza Stark Gene: relb has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1905 RELB Zornitza Stark gene: RELB was added
gene: RELB was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RELB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RELB were set to 7834753; 26385063
Phenotypes for gene: RELB were set to Immunodeficiency 53, MIM# 617585; T cells: normal number, poor diversity, poor function; recurrent infections
Review for gene: RELB was set to AMBER
Added comment: Single family reported, functional data.
Sources: Expert list
Mendeliome v0.1901 NSMCE2 Tiong Tan Classified gene: NSMCE2 as Amber List (moderate evidence)
Mendeliome v0.1901 NSMCE2 Tiong Tan Gene: nsmce2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1900 NSMCE2 Tiong Tan gene: NSMCE2 was added
gene: NSMCE2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NSMCE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSMCE2 were set to 25105364
Phenotypes for gene: NSMCE2 were set to SECKEL SYNDROME 10
Penetrance for gene: NSMCE2 were set to Complete
Review for gene: NSMCE2 was set to AMBER
Added comment: Biallelic hypomorphic variants in two unrelated women with microcephalic primordial dwarfism, insulin-resistant diabetes, fatty liver, and hypertriglyceridemia developing in childhood; and primary gonadal failure. Good quality functional evidence. No additional confirmatory cases since 2014 publication
Sources: Literature
Mendeliome v0.1899 PLEKHA5 Zornitza Stark Classified gene: PLEKHA5 as Amber List (moderate evidence)
Mendeliome v0.1899 PLEKHA5 Zornitza Stark Gene: plekha5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1898 PLEKHA5 Zornitza Stark reviewed gene: PLEKHA5: Rating: AMBER; Mode of pathogenicity: None; Publications: 29805042; Phenotypes: cleft lip, cleft palate; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1898 TRPA1 Zornitza Stark Gene: trpa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1898 TRPA1 Zornitza Stark Classified gene: TRPA1 as Amber List (moderate evidence)
Mendeliome v0.1898 TRPA1 Zornitza Stark Gene: trpa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1897 TRPA1 Zornitza Stark gene: TRPA1 was added
gene: TRPA1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TRPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPA1 were set to 20547126; 16564016; 21468319; 28314413; 24778270; 24564660; 20718100
Phenotypes for gene: TRPA1 were set to Episodic pain syndrome, familial, 1, MIM# 615040
Review for gene: TRPA1 was set to AMBER
Added comment: Single family and a lot of functional data.
Sources: Expert list
Mendeliome v0.1895 CNKSR1 Zornitza Stark Gene: cnksr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1895 CNKSR1 Zornitza Stark Classified gene: CNKSR1 as Amber List (moderate evidence)
Mendeliome v0.1895 CNKSR1 Zornitza Stark Gene: cnksr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1894 CNKSR1 Zornitza Stark gene: CNKSR1 was added
gene: CNKSR1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CNKSR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNKSR1 were set to 30450701; 30237576; 21937992
Phenotypes for gene: CNKSR1 were set to Intellectual disability
Review for gene: CNKSR1 was set to AMBER
Added comment: Three families reported, two as part of large cohorts reporting multiple novel genes. Note the family reported in PMID 30450701 appears to be the same family as reported in PMID 21937992. Some functional data in PMID 30450701, including Drosophila model.
Sources: Expert Review
Mendeliome v0.1893 FRMD4A Zornitza Stark Gene: frmd4a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1893 FRMD4A Zornitza Stark Classified gene: FRMD4A as Amber List (moderate evidence)
Mendeliome v0.1893 FRMD4A Zornitza Stark Gene: frmd4a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1892 FRMD4A Zornitza Stark gene: FRMD4A was added
gene: FRMD4A was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: FRMD4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRMD4A were set to 25388005; 30214071
Phenotypes for gene: FRMD4A were set to Intellectual disability; microcephaly; Corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia, MIM# 616819
Review for gene: FRMD4A was set to AMBER
Added comment: Single Bedouin Israeli family reported with homozygous variant initially. Good segregation data. No functional data. Another family reported as part of a large consanguineous microcephaly cohort, different variant.
Sources: Expert Review
Mendeliome v0.1881 FBXO38 Zornitza Stark Gene: fbxo38 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1878 FBXO38 Zornitza Stark Classified gene: FBXO38 as Amber List (moderate evidence)
Mendeliome v0.1878 FBXO38 Zornitza Stark Gene: fbxo38 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1877 FBXO38 Zornitza Stark reviewed gene: FBXO38: Rating: AMBER; Mode of pathogenicity: None; Publications: 24207122, 31420593; Phenotypes: Neuronopathy, distal hereditary motor, type IID, 615575, dHMN/dSMA; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1875 DGAT2 Zornitza Stark Gene: dgat2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1875 DGAT2 Zornitza Stark Classified gene: DGAT2 as Amber List (moderate evidence)
Mendeliome v0.1875 DGAT2 Zornitza Stark Gene: dgat2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1874 DGAT2 Zornitza Stark gene: DGAT2 was added
gene: DGAT2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: DGAT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DGAT2 were set to 26786738
Phenotypes for gene: DGAT2 were set to axonal Charcot-Marie-Tooth disease
Review for gene: DGAT2 was set to AMBER
Added comment: Single family (father and son) reported, with supporting in vitro functional assays and a zebrafish model.
Sources: Expert Review
Mendeliome v0.1837 GNB2 Sue White Classified gene: GNB2 as Amber List (moderate evidence)
Mendeliome v0.1837 GNB2 Sue White Gene: gnb2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1836 GNB2 Sue White gene: GNB2 was added
gene: GNB2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNB2 were set to 31698099
Phenotypes for gene: GNB2 were set to intellectual disability; dysmorphic features
Penetrance for gene: GNB2 were set to Complete
Review for gene: GNB2 was set to AMBER
Added comment: single report of patient with de novo missense variant in GNB2 and intellectual disability. Emerging evidence of other de no missense variants in GNB2 and ID
Sources: Literature
Mendeliome v0.1830 CBS Zornitza Stark Phenotypes for gene: CBS were changed from to Homocystinuria, B6-responsive and nonresponsive types, 236200; Thrombosis, hyperhomocysteinemic, 236200
Mendeliome v0.1827 CBS Kristin Rigbye reviewed gene: CBS: Rating: GREEN; Mode of pathogenicity: None; Publications: 7506602, 10338090; Phenotypes: Homocystinuria, B6-responsive and nonresponsive types, 236200, Thrombosis, hyperhomocysteinemic, 236200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1824 SLC25A21 Zornitza Stark Gene: slc25a21 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1824 SLC25A21 Zornitza Stark Classified gene: SLC25A21 as Amber List (moderate evidence)
Mendeliome v0.1824 SLC25A21 Zornitza Stark Gene: slc25a21 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1823 SLC25A21 Zornitza Stark gene: SLC25A21 was added
gene: SLC25A21 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: SLC25A21 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A21 were set to 29517768
Phenotypes for gene: SLC25A21 were set to Mitochondrial DNA depletion syndrome-18, MIM#618811
Review for gene: SLC25A21 was set to AMBER
Added comment: One case with a homozygous variant and functional assays showing mitochondrial dysfunction.
Sources: NHS GMS
Mendeliome v0.1822 SLC25A10 Zornitza Stark Gene: slc25a10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1822 SLC25A10 Zornitza Stark Classified gene: SLC25A10 as Amber List (moderate evidence)
Mendeliome v0.1822 SLC25A10 Zornitza Stark Gene: slc25a10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1821 SLC25A10 Zornitza Stark gene: SLC25A10 was added
gene: SLC25A10 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: SLC25A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A10 were set to 29211846
Phenotypes for gene: SLC25A10 were set to Intractable epileptic encephalopathy
Review for gene: SLC25A10 was set to AMBER
Added comment: One case with intractable epileptic encephalopathy with complex I deficiency, with biallelic variants. Yeast SLC25A10 ortholog lack-of-function causes impairment in mitochondrial respiration, reduced mtDNA copy number and oxidative stress vulnerability.
Sources: NHS GMS
Mendeliome v0.1816 PTCD3 Zornitza Stark Gene: ptcd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1816 PTCD3 Zornitza Stark Classified gene: PTCD3 as Amber List (moderate evidence)
Mendeliome v0.1816 PTCD3 Zornitza Stark Gene: ptcd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1815 PTCD3 Zornitza Stark gene: PTCD3 was added
gene: PTCD3 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: PTCD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTCD3 were set to 30607703; 19427859
Phenotypes for gene: PTCD3 were set to Intellectual disability; optic atrophy; Leigh-like syndrome
Review for gene: PTCD3 was set to AMBER
Added comment: One compound heterozygote case and functional assays. Essential subunit of oxidative phosphorylation (OXPHOS) complexes.
Sources: NHS GMS
Mendeliome v0.1810 OXA1L Zornitza Stark Gene: oxa1l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1810 OXA1L Zornitza Stark Classified gene: OXA1L as Amber List (moderate evidence)
Mendeliome v0.1810 OXA1L Zornitza Stark Gene: oxa1l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1809 OXA1L Zornitza Stark gene: OXA1L was added
gene: OXA1L was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: OXA1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OXA1L were set to 30201738; 16435202
Phenotypes for gene: OXA1L were set to Encephalopathy; hypotonia; developmental delay
Review for gene: OXA1L was set to AMBER
Added comment: Single family reported with biochemical and molecular analyses of patient skeletal muscle and fibroblasts. In vitro functional assays in human cell lines, Drosophila model, and yeast-based assays. Loss of function affects oxidative phosphorylation complexes IV and V.
Sources: NHS GMS
Mendeliome v0.1808 NSUN3 Zornitza Stark Gene: nsun3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1808 NSUN3 Zornitza Stark Classified gene: NSUN3 as Amber List (moderate evidence)
Mendeliome v0.1808 NSUN3 Zornitza Stark Gene: nsun3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1807 NSUN3 Zornitza Stark gene: NSUN3 was added
gene: NSUN3 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: NSUN3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSUN3 were set to 27356879
Phenotypes for gene: NSUN3 were set to combined mitochondrial respiratory chain complex deficiency
Review for gene: NSUN3 was set to AMBER
Added comment: A single compound heterozygous case. Patient-derived fibroblasts exhibited severe defects in mitochondrial translation that can be rescued by exogenous expression of NSun3. In vitro functional assays also conducted.
Sources: NHS GMS
Mendeliome v0.1806 NDUFB10 Zornitza Stark Gene: ndufb10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1806 NDUFB10 Zornitza Stark Classified gene: NDUFB10 as Amber List (moderate evidence)
Mendeliome v0.1806 NDUFB10 Zornitza Stark Gene: ndufb10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1805 NDUFB10 Zornitza Stark gene: NDUFB10 was added
gene: NDUFB10 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: NDUFB10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFB10 were set to 28040730; 32025618
Phenotypes for gene: NDUFB10 were set to fatal infantile lactic acidosis; cardiomyopathy
Review for gene: NDUFB10 was set to AMBER
Added comment: Single compound heterozygote case and mitochondrial phenotype. Assays of respiratory chain enzyme activities and functions in patient tissues/fibroblasts and in vitro functional assays. Plant model system supporting mitochondrial complex I dysfunction.
Sources: NHS GMS
Mendeliome v0.1803 MRPS14 Zornitza Stark Gene: mrps14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1803 MRPS14 Zornitza Stark Classified gene: MRPS14 as Amber List (moderate evidence)
Mendeliome v0.1803 MRPS14 Zornitza Stark Gene: mrps14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1802 MRPS14 Zornitza Stark edited their review of gene: MRPS14: Changed rating: AMBER; Changed phenotypes: Combined oxidative phosphorylation deficiency 38, MIM# 618378
Mendeliome v0.1802 MRM2 Zornitza Stark Gene: mrm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1802 MRM2 Zornitza Stark Classified gene: MRM2 as Amber List (moderate evidence)
Mendeliome v0.1802 MRM2 Zornitza Stark Gene: mrm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1801 MRM2 Zornitza Stark gene: MRM2 was added
gene: MRM2 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: MRM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRM2 were set to 28973171
Phenotypes for gene: MRM2 were set to MELAS-like
Review for gene: MRM2 was set to AMBER
Added comment: Single individual reported plus functional data. MRM2 encodes an enzyme responsible for 2'-O-methyl modification at position U1369 in the human mitochondrial 16S rRNA.
Sources: NHS GMS
Mendeliome v0.1781 TFAM Zornitza Stark gene: TFAM was added
gene: TFAM was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: TFAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TFAM were set to 27448789; 29021295; 9500544
Phenotypes for gene: TFAM were set to Mitochondrial DNA depletion syndrome 15 (hepatocerebral type) MIM#617156
Review for gene: TFAM was set to AMBER
Added comment: One consanguineous family segregates a homozygous variant. Tfam knockout mouse has a mitochondrial cardiomyopathy phenotype and severe mtDNA depletion with abolished oxidative phosphorylation.
Sources: NHS GMS
Mendeliome v0.1780 TIMM22 Zornitza Stark Gene: timm22 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1780 TIMM22 Zornitza Stark Classified gene: TIMM22 as Amber List (moderate evidence)
Mendeliome v0.1780 TIMM22 Zornitza Stark Gene: timm22 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1779 TIMM22 Zornitza Stark gene: TIMM22 was added
gene: TIMM22 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: TIMM22 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TIMM22 were set to 30452684
Phenotypes for gene: TIMM22 were set to mitochondrial myopathy; hypotonia; gastroesophageal reflux disease
Review for gene: TIMM22 was set to AMBER
Added comment: One compound heterozygote case identified with supporting in vitro and patient cell functional assays.
Sources: NHS GMS
Mendeliome v0.1778 TIMMDC1 Zornitza Stark Gene: timmdc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1778 TIMMDC1 Zornitza Stark Classified gene: TIMMDC1 as Amber List (moderate evidence)
Mendeliome v0.1778 TIMMDC1 Zornitza Stark Gene: timmdc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1777 TIMMDC1 Zornitza Stark gene: TIMMDC1 was added
gene: TIMMDC1 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: TIMMDC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TIMMDC1 were set to 28604674; 30981218
Phenotypes for gene: TIMMDC1 were set to Mitochondrial complex I deficiency, nuclear type 31 MIM#618251
Review for gene: TIMMDC1 was set to AMBER
Added comment: A deep intronic variant (c.597-1340A>G, only detectable by WGS) that causes a splicing aberration was identified in a homozygous state in 3 unrelated cases from different ethnic backgrounds. A patient with Leigh-like syndrome had a homozygous stopgain variant in PDHX and a homozygous stopgain variant in TIMMDC1 (p.Arg225*). The TIMMDC1 mutant protein could still rescue complex I assembly in TIMMDC1 knockout cells and the patient’s clinical phenotype was not clearly distinct from that of other patients with the same PDHX defect.
Sources: NHS GMS
Mendeliome v0.1776 TMEM65 Zornitza Stark Gene: tmem65 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1776 TMEM65 Zornitza Stark Classified gene: TMEM65 as Amber List (moderate evidence)
Mendeliome v0.1776 TMEM65 Zornitza Stark Gene: tmem65 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1775 TMEM65 Zornitza Stark gene: TMEM65 was added
gene: TMEM65 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: TMEM65 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM65 were set to 28295037
Phenotypes for gene: TMEM65 were set to Mitochondrial encephalomyopathy
Review for gene: TMEM65 was set to AMBER
Added comment: One homozygous case with a mitochondrial encephalomyopathy and functional assays showing the protein is important for mitochondrial respiration and mtDNA copy number maintenance.
Sources: NHS GMS
Mendeliome v0.1774 ADAM17 Lauren Akesson reviewed gene: ADAM17: Rating: AMBER; Mode of pathogenicity: None; Publications: 22010916, 25804906, 21041656, 22236242; Phenotypes: Inflammatory neonatal-onset skin and bowel disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1770 YME1L1 Zornitza Stark Gene: yme1l1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1770 YME1L1 Zornitza Stark Classified gene: YME1L1 as Amber List (moderate evidence)
Mendeliome v0.1770 YME1L1 Zornitza Stark Gene: yme1l1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1769 YME1L1 Zornitza Stark gene: YME1L1 was added
gene: YME1L1 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: YME1L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YME1L1 were set to 30544562; 27495975
Phenotypes for gene: YME1L1 were set to Optic atrophy 11, MIM#617302
Review for gene: YME1L1 was set to AMBER
Added comment: One consanguineous family with a homozygous variant and functional assays. YME1L leads to mitochondrial fragmentation and severely disorganized and attenuated cristae architecture in in vitro functional assays.
Sources: NHS GMS
Mendeliome v0.1765 UQCRQ Zornitza Stark Gene: uqcrq has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1762 UQCRQ Zornitza Stark Classified gene: UQCRQ as Amber List (moderate evidence)
Mendeliome v0.1762 UQCRQ Zornitza Stark Gene: uqcrq has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1761 UQCRQ Zornitza Stark reviewed gene: UQCRQ: Rating: AMBER; Mode of pathogenicity: None; Publications: 18439546; Phenotypes: Mitochondrial complex III deficiency, nuclear type 4, MIM# 615159; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1761 UQCRC2 Zornitza Stark Gene: uqcrc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1758 UQCRC2 Zornitza Stark Classified gene: UQCRC2 as Amber List (moderate evidence)
Mendeliome v0.1758 UQCRC2 Zornitza Stark Gene: uqcrc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1757 UQCRC2 Zornitza Stark reviewed gene: UQCRC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 28275242, 23281071; Phenotypes: Mitochondrial complex III deficiency, nuclear type 5, MIM# 615160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1757 UQCC3 Zornitza Stark Gene: uqcc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1754 UQCC3 Zornitza Stark Classified gene: UQCC3 as Amber List (moderate evidence)
Mendeliome v0.1754 UQCC3 Zornitza Stark Gene: uqcc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1753 UQCC3 Zornitza Stark reviewed gene: UQCC3: Rating: AMBER; Mode of pathogenicity: None; Publications: 25008109, 28804536; Phenotypes: Mitochondrial complex III deficiency, nuclear type 9, MIM# 616111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1753 TXN2 Zornitza Stark Gene: txn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1753 TXN2 Zornitza Stark Phenotypes for gene: TXN2 were changed from to Combined oxidative phosphorylation deficiency 29, MIM# 616811
Mendeliome v0.1750 TXN2 Zornitza Stark Classified gene: TXN2 as Amber List (moderate evidence)
Mendeliome v0.1750 TXN2 Zornitza Stark Gene: txn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1749 TXN2 Zornitza Stark reviewed gene: TXN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 26626369, 12529397; Phenotypes: Combined oxidative phosphorylation deficiency 29, MIM# 616811; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1749 TARS2 Zornitza Stark Gene: tars2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1749 TARS2 Zornitza Stark Phenotypes for gene: TARS2 were changed from to Combined oxidative phosphorylation deficiency 21, MIM# 615918
Mendeliome v0.1746 TARS2 Zornitza Stark Classified gene: TARS2 as Amber List (moderate evidence)
Mendeliome v0.1746 TARS2 Zornitza Stark Gene: tars2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1745 TARS2 Zornitza Stark reviewed gene: TARS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24827421, 26811336; Phenotypes: Combined oxidative phosphorylation deficiency 21, MIM# 615918; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1736 NDUFA4 Zornitza Stark Gene: ndufa4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1733 NDUFA4 Zornitza Stark Classified gene: NDUFA4 as Amber List (moderate evidence)
Mendeliome v0.1733 NDUFA4 Zornitza Stark Gene: ndufa4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1732 NDUFA4 Zornitza Stark reviewed gene: NDUFA4: Rating: AMBER; Mode of pathogenicity: None; Publications: 30361421, 28988874, 23746447; Phenotypes: Leigh syndrome, Complex IV deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1683 RSPRY1 Zornitza Stark Gene: rspry1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1680 RSPRY1 Zornitza Stark Classified gene: RSPRY1 as Amber List (moderate evidence)
Mendeliome v0.1680 RSPRY1 Zornitza Stark Gene: rspry1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1679 RSPRY1 Zornitza Stark reviewed gene: RSPRY1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26365341; Phenotypes: Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, 616585; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1679 RPS23 Zornitza Stark Gene: rps23 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1675 RPS23 Zornitza Stark Classified gene: RPS23 as Amber List (moderate evidence)
Mendeliome v0.1675 RPS23 Zornitza Stark Gene: rps23 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1674 RPS23 Zornitza Stark reviewed gene: RPS23: Rating: AMBER; Mode of pathogenicity: None; Publications: 28257692; Phenotypes: Brachycephaly, trichomegaly, and developmental delay, MIM# 617412; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1673 KANK1 Zornitza Stark changed review comment from: Comment on list classification: Amber for nephrotic after discussion with Chirag Patel.; to: Comment on list classification: Red for nephrotic after discussion with Chirag Patel.
Mendeliome v0.1671 FUT2 Zornitza Stark Phenotypes for gene: FUT2 were changed from to [Bombay phenotype, digenic] 616754; {Norwalk virus infection, resistance to}; {Vitamin B12 plasma level QTL1} 612542
Mendeliome v0.1669 FUT2 Zornitza Stark reviewed gene: FUT2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: [Bombay phenotype, digenic] 616754, {Norwalk virus infection, resistance to}, {Vitamin B12 plasma level QTL1} 612542; Mode of inheritance: None
Mendeliome v0.1669 HMGA2 Zornitza Stark Gene: hmga2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1666 HMGA2 Zornitza Stark Classified gene: HMGA2 as Amber List (moderate evidence)
Mendeliome v0.1666 HMGA2 Zornitza Stark Gene: hmga2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1665 HMGA2 Zornitza Stark reviewed gene: HMGA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29655892, 25809938; Phenotypes: Silver-Russel syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1650 BPTF Zornitza Stark Phenotypes for gene: BPTF were changed from to Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies AD, MIM#617755
Mendeliome v0.1637 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1637 NUDT2 Zornitza Stark Classified gene: NUDT2 as Amber List (moderate evidence)
Mendeliome v0.1637 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1636 NUDT2 Zornitza Stark gene: NUDT2 was added
gene: NUDT2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NUDT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDT2 were set to 27431290; 30059600
Phenotypes for gene: NUDT2 were set to Muscular hypotonia; Global developmental delay; Intellectual disability
Review for gene: NUDT2 was set to AMBER
Added comment: 7 affected individuals from 4 Saudi families, with same homozygous truncating variant.
Sources: Expert list
Mendeliome v0.1635 BPTF Michelle Torres reviewed gene: BPTF: Rating: GREEN; Mode of pathogenicity: None; Publications: 28942966; Phenotypes: Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1621 ZBTB16 Zornitza Stark Gene: zbtb16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1618 ZBTB16 Zornitza Stark Classified gene: ZBTB16 as Amber List (moderate evidence)
Mendeliome v0.1618 ZBTB16 Zornitza Stark Gene: zbtb16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1617 ZBTB16 Zornitza Stark reviewed gene: ZBTB16: Rating: AMBER; Mode of pathogenicity: None; Publications: 18611983; Phenotypes: Skeletal defects, genital hypoplasia, and mental retardation, OMIM #612447; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1617 ZBTB11 Zornitza Stark Gene: zbtb11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1614 ZBTB11 Zornitza Stark Classified gene: ZBTB11 as Amber List (moderate evidence)
Mendeliome v0.1614 ZBTB11 Zornitza Stark Gene: zbtb11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1613 ZBTB11 Zornitza Stark reviewed gene: ZBTB11: Rating: AMBER; Mode of pathogenicity: None; Publications: 29893856; Phenotypes: Intellectual developmental disorder, autosomal recessive 69, OMIM #618383; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1561 TNIK Zornitza Stark Gene: tnik has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1558 TNIK Zornitza Stark Classified gene: TNIK as Amber List (moderate evidence)
Mendeliome v0.1558 TNIK Zornitza Stark Gene: tnik has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1557 TNIK Zornitza Stark reviewed gene: TNIK: Rating: AMBER; Mode of pathogenicity: None; Publications: 27106596, 23035106; Phenotypes: Mental retardation, autosomal recessive 54, MIM# 617028; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1552 TMEM260 Zornitza Stark Gene: tmem260 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1549 TMEM260 Zornitza Stark Classified gene: TMEM260 as Amber List (moderate evidence)
Mendeliome v0.1549 TMEM260 Zornitza Stark Gene: tmem260 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1548 TMEM260 Zornitza Stark reviewed gene: TMEM260: Rating: AMBER; Mode of pathogenicity: None; Publications: 28318500; Phenotypes: Structural heart defects and renal anomalies syndrome, MIM# 617478; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1548 TKT Zornitza Stark Gene: tkt has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1545 TKT Zornitza Stark Classified gene: TKT as Amber List (moderate evidence)
Mendeliome v0.1545 TKT Zornitza Stark Gene: tkt has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1544 TKT Zornitza Stark reviewed gene: TKT: Rating: AMBER; Mode of pathogenicity: None; Publications: 27259054; Phenotypes: Short stature, developmental delay, and congenital heart defects, OMIM #617044; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1537 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1534 TBC1D7 Zornitza Stark Classified gene: TBC1D7 as Amber List (moderate evidence)
Mendeliome v0.1534 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1533 TBC1D7 Zornitza Stark reviewed gene: TBC1D7: Rating: AMBER; Mode of pathogenicity: None; Publications: 24515783, 23687350; Phenotypes: Macrocephaly/megalencephaly syndrome, autosomal recessive, MIM# 248000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1533 TAF2 Zornitza Stark Gene: taf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1530 TAF2 Zornitza Stark Classified gene: TAF2 as Amber List (moderate evidence)
Mendeliome v0.1530 TAF2 Zornitza Stark Gene: taf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1529 TAF2 Zornitza Stark reviewed gene: TAF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 21937992, 22633631, 26350204; Phenotypes: Mental retardation, autosomal recessive 40, MIM# 615599; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1529 TAF13 Zornitza Stark Gene: taf13 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1526 TAF13 Zornitza Stark Classified gene: TAF13 as Amber List (moderate evidence)
Mendeliome v0.1526 TAF13 Zornitza Stark Gene: taf13 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1525 TAF13 Zornitza Stark reviewed gene: TAF13: Rating: AMBER; Mode of pathogenicity: None; Publications: 28257693; Phenotypes: Mental retardation, autosomal recessive 60, MIM# 617432; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1454 SLIT2 Zornitza Stark Gene: slit2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1451 SLIT2 Zornitza Stark Classified gene: SLIT2 as Amber List (moderate evidence)
Mendeliome v0.1451 SLIT2 Zornitza Stark Gene: slit2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1450 SLIT2 Zornitza Stark reviewed gene: SLIT2: Rating: AMBER; Mode of pathogenicity: None; Publications: 26026792, 15130495; Phenotypes: CAKUT; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1450 CEL Zornitza Stark Gene: cel has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1447 CEL Zornitza Stark Classified gene: CEL as Amber List (moderate evidence)
Mendeliome v0.1447 CEL Zornitza Stark Gene: cel has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1446 CEL Zornitza Stark reviewed gene: CEL: Rating: AMBER; Mode of pathogenicity: None; Publications: 24062244, 21784842, 19760265, 18544793, 17989309, 16369531, 29233499, 27650499; Phenotypes: Maturity-onset diabetes of the young, type VIII; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1439 MYL1 Bryony Thompson Classified gene: MYL1 as Amber List (moderate evidence)
Mendeliome v0.1439 MYL1 Bryony Thompson Gene: myl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1438 MYL1 Bryony Thompson gene: MYL1 was added
gene: MYL1 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: MYL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYL1 were set to 30215711
Phenotypes for gene: MYL1 were set to Myopathy, congenital, with fast-twitch (type II) fiber atrophy MIM#618414
Review for gene: MYL1 was set to AMBER
Added comment: Two probands with congenital myopathy and a zebrafish model. Probably need one more family to push it over the line.
Sources: NHS GMS
Mendeliome v0.1418 PNPT1 Zornitza Stark Phenotypes for gene: PNPT1 were changed from to Combined oxidative phosphorylation deficiency 13 (MIM#614932); Deafness, autosomal recessive 70 (MIM#614934)
Mendeliome v0.1415 PNPT1 Crystle Lee reviewed gene: PNPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:31752325, PMID: 30244537, PMID: 28594066, PMID: 28645153; Phenotypes: Combined oxidative phosphorylation deficiency 13 (MIM#614932), Deafness, autosomal recessive 70 (MIM#614934); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1386 SHROOM4 Zornitza Stark Gene: shroom4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1383 SHROOM4 Zornitza Stark Classified gene: SHROOM4 as Amber List (moderate evidence)
Mendeliome v0.1383 SHROOM4 Zornitza Stark Gene: shroom4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1382 SHROOM4 Zornitza Stark reviewed gene: SHROOM4: Rating: AMBER; Mode of pathogenicity: None; Publications: 16249884, 26740508; Phenotypes: Stocco dos Santos X-linked mental retardation syndrome, 300434, Intellectual disability; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1382 F2 Zornitza Stark Phenotypes for gene: F2 were changed from to {Pregnancy loss, recurrent, susceptibility to, 2} 614390 AD; {Stroke, ischemic, susceptibility to} 601367 Mu; Dysprothrombinemia 613679 AR; Hypoprothrombinemia 613679 AR; Thrombophilia due to thrombin defect 188050 AD
Mendeliome v0.1379 F2 Zornitza Stark reviewed gene: F2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30297698; Phenotypes: {Pregnancy loss, recurrent, susceptibility to, 2} 614390 AD, {Stroke, ischemic, susceptibility to} 601367 Mu, Dysprothrombinemia 613679 AR, Hypoprothrombinemia 613679 AR, Thrombophilia due to thrombin defect 188050 AD; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1372 SOX3 Zornitza Stark Gene: sox3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1369 SOX3 Zornitza Stark Classified gene: SOX3 as Amber List (moderate evidence)
Mendeliome v0.1369 SOX3 Zornitza Stark Gene: sox3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1368 SOX3 Zornitza Stark reviewed gene: SOX3: Rating: AMBER; Mode of pathogenicity: None; Publications: 29175558, 30125608, 12428212, 15800844; Phenotypes: Mental retardation, X-linked, with isolated growth hormone deficiency, MIM#300123, Panhypopituitarism, X-linked, MIM#312000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1368 AKT1 Zornitza Stark Gene: akt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1364 AKT1 Zornitza Stark Classified gene: AKT1 as Amber List (moderate evidence)
Mendeliome v0.1364 AKT1 Zornitza Stark Gene: akt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1357 AKT1 Elena Savva reviewed gene: AKT1: Rating: AMBER; 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: PMID: 23246288; Phenotypes: Cowden syndrome 6, Proteus syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.1348 PLEKHG2 Zornitza Stark Classified gene: PLEKHG2 as Amber List (moderate evidence)
Mendeliome v0.1348 PLEKHG2 Zornitza Stark Gene: plekhg2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1347 PLEKHG2 Zornitza Stark edited their review of gene: PLEKHG2: Added comment: Further family identified, promote to Amber.; Changed rating: AMBER; Changed publications: 26539891, 24001768, 26573021; Changed phenotypes: Leukodystrophy and acquired microcephaly with or without dystonia, MIM# 616763
Mendeliome v0.1325 MAP3K20 Bryony Thompson gene: MAP3K20 was added
gene: MAP3K20 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MAP3K20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAP3K20 were set to 27816943; 26755636
Phenotypes for gene: MAP3K20 were set to Centronuclear myopathy 6 with fiber-type disproportion MIM#617760; Split-foot malformation with mesoaxial polydactyly MIM#616890
Review for gene: MAP3K20 was set to GREEN
Added comment: 3 unrelated consanguineous families homozygous for 3 different variants with centronuclear myopathy, and at least 2 families reported with split-foot malformation. Null mouse model is embryonic lethal due to severe cardiac edema and growth retardation. Gene alias of ZAK used in the published studies.
Sources: Expert list
Mendeliome v0.1320 LNPK Zornitza Stark Gene: lnpk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1317 LNPK Zornitza Stark Classified gene: LNPK as Amber List (moderate evidence)
Mendeliome v0.1317 LNPK Zornitza Stark Gene: lnpk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1316 LNPK Zornitza Stark reviewed gene: LNPK: Rating: AMBER; Mode of pathogenicity: None; Publications: 30032983; Phenotypes: Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, MIM# 618090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1292 PLEC Zornitza Stark Phenotypes for gene: PLEC were changed from to ?Epidermolysis bullosa simplex with nail dystrophy, MIM# 616487; Epidermolysis bullosa simplex with muscular dystrophy, MIM# 226670; Epidermolysis bullosa simplex with pyloric atresia, MIM# 612138; Epidermolysis bullosa simplex, Ogna type MIM#131950; Muscular dystrophy, limb-girdle, autosomal recessive 17, MIM# 613723
Mendeliome v0.1289 PLEC Elena Savva reviewed gene: PLEC: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22144912; Phenotypes: ?Epidermolysis bullosa simplex with nail dystrophy, Epidermolysis bullosa simplex with muscular dystrophy, Epidermolysis bullosa simplex with pyloric atresia, Epidermolysis bullosa simplex, Ogna type, Muscular dystrophy, limb-girdle; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.1271 HDAC4 Zornitza Stark Gene: hdac4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1267 HDAC4 Zornitza Stark Classified gene: HDAC4 as Amber List (moderate evidence)
Mendeliome v0.1267 HDAC4 Zornitza Stark Gene: hdac4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1266 UBR4 Zornitza Stark Gene: ubr4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1263 UBR4 Zornitza Stark Classified gene: UBR4 as Amber List (moderate evidence)
Mendeliome v0.1263 UBR4 Zornitza Stark Gene: ubr4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1262 UBR4 Zornitza Stark reviewed gene: UBR4: Rating: AMBER; Mode of pathogenicity: None; Publications: 29062094, 23982692, 28600779; Phenotypes: Episodic ataxia, progressive neurological deterioration; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1262 HDAC4 Elena Savva reviewed gene: HDAC4: Rating: AMBER; Mode of pathogenicity: Other; Publications: PMID: 24715439, 20691407, 31209962; Phenotypes: Brachydactyly mental retardation syndrome, Brachydactyly without intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.1255 NSF Zornitza Stark Gene: nsf has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1255 NSF Zornitza Stark Classified gene: NSF as Amber List (moderate evidence)
Mendeliome v0.1255 NSF Zornitza Stark Gene: nsf has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1254 NSF Zornitza Stark gene: NSF was added
gene: NSF was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NSF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NSF were set to 31675180
Phenotypes for gene: NSF were set to Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability
Review for gene: NSF was set to AMBER
Added comment: Two individuals reported with de novo missense variants in this gene.
Sources: Literature
Mendeliome v0.1237 SASS6 Zornitza Stark Gene: sass6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1234 SASS6 Zornitza Stark Classified gene: SASS6 as Amber List (moderate evidence)
Mendeliome v0.1234 SASS6 Zornitza Stark Gene: sass6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1233 SASS6 Zornitza Stark reviewed gene: SASS6: Rating: AMBER; Mode of pathogenicity: None; Publications: 24951542, 30639237; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM# 616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1224 CNTN1 Zornitza Stark Gene: cntn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1221 CNTN1 Zornitza Stark Classified gene: CNTN1 as Amber List (moderate evidence)
Mendeliome v0.1221 CNTN1 Zornitza Stark Gene: cntn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1220 CNTN1 Zornitza Stark reviewed gene: CNTN1: Rating: AMBER; Mode of pathogenicity: None; Publications: 19026398; Phenotypes: Myopathy, congenital, Compton-North 612540; Mode of inheritance: None
Mendeliome v0.1216 MRPS7 Zornitza Stark Phenotypes for gene: MRPS7 were changed from to Combined oxidative phosphorylation deficiency 34, MIM# 617872
Mendeliome v0.1212 MRPS7 Zornitza Stark reviewed gene: MRPS7: Rating: RED; Mode of pathogenicity: None; Publications: 25556185; Phenotypes: Combined oxidative phosphorylation deficiency 34, MIM# 617872; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1212 MRPS23 Zornitza Stark Phenotypes for gene: MRPS23 were changed from to Hepatic disease; Combined respiratory chain complex deficiencies
Mendeliome v0.1208 MRPS23 Zornitza Stark reviewed gene: MRPS23: Rating: RED; Mode of pathogenicity: None; Publications: 26741492; Phenotypes: Hepatic disease, Combined respiratory chain complex deficiencies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1204 LYRM4 Zornitza Stark Gene: lyrm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1204 LYRM4 Zornitza Stark Phenotypes for gene: LYRM4 were changed from to Combined oxidative phosphorylation deficiency 19, MIM# 615595
Mendeliome v0.1201 LYRM4 Zornitza Stark Classified gene: LYRM4 as Amber List (moderate evidence)
Mendeliome v0.1201 LYRM4 Zornitza Stark Gene: lyrm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1200 LYRM4 Zornitza Stark reviewed gene: LYRM4: Rating: AMBER; Mode of pathogenicity: None; Publications: 23814038, 31497476; Phenotypes: Combined oxidative phosphorylation deficiency 19, MIM# 615595; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1185 FIBP Zornitza Stark Gene: fibp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1182 FIBP Zornitza Stark Classified gene: FIBP as Amber List (moderate evidence)
Mendeliome v0.1182 FIBP Zornitza Stark Gene: fibp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1181 FIBP Zornitza Stark reviewed gene: FIBP: Rating: AMBER; Mode of pathogenicity: None; Publications: 26660953, 27183861; Phenotypes: Thauvin-Robinet-Faivre syndrome, MIM#617107; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1177 RASA2 Sebastian Lunke Gene: rasa2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1176 RASA2 Sebastian Lunke Classified gene: RASA2 as Amber List (moderate evidence)
Mendeliome v0.1176 RASA2 Sebastian Lunke Gene: rasa2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1175 RASA2 Sebastian Lunke reviewed gene: RASA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 25049390, 30311384; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1175 TKFC Zornitza Stark Gene: tkfc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1175 TKFC Zornitza Stark Classified gene: TKFC as Amber List (moderate evidence)
Mendeliome v0.1175 TKFC Zornitza Stark Gene: tkfc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1174 TKFC Zornitza Stark gene: TKFC was added
gene: TKFC was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TKFC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TKFC were set to 32004446
Phenotypes for gene: TKFC were set to Developmental delay; cataracts; liver dysfunction
Review for gene: TKFC was set to AMBER
Added comment: Two unrelated individuals reported.
Sources: Literature
Mendeliome v0.1158 MYOM1 Zornitza Stark Gene: myom1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1155 MYOM1 Zornitza Stark Classified gene: MYOM1 as Amber List (moderate evidence)
Mendeliome v0.1155 MYOM1 Zornitza Stark Gene: myom1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1154 MYOM1 Zornitza Stark reviewed gene: MYOM1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27600940, 26656175, 21256114; Phenotypes: Hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1150 DIP2B Zornitza Stark Gene: dip2b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1146 DIP2B Zornitza Stark Classified gene: DIP2B as Amber List (moderate evidence)
Mendeliome v0.1146 DIP2B Zornitza Stark Gene: dip2b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1145 DIP2B Zornitza Stark reviewed gene: DIP2B: Rating: AMBER; 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: 17236128; Phenotypes: Mental retardation, FRA12A type, MIM# 136630; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1102 CLDN10 Zornitza Stark Phenotypes for gene: CLDN10 were changed from to HELIX syndrome MIM#617671; hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia (HELIX)
Mendeliome v0.1100 CLDN10 Zornitza Stark reviewed gene: CLDN10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: HELIX syndrome MIM#617671, hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia (HELIX); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1092 CASP14 Zornitza Stark Gene: casp14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1092 CASP14 Zornitza Stark Classified gene: CASP14 as Amber List (moderate evidence)
Mendeliome v0.1092 CASP14 Zornitza Stark Gene: casp14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1091 CASP14 Zornitza Stark gene: CASP14 was added
gene: CASP14 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CASP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CASP14 were set to 27494380; 23014340; 17515931
Phenotypes for gene: CASP14 were set to Ichthyosis, congenital, autosomal recessive 12 MIM#617320
Review for gene: CASP14 was set to AMBER
Added comment: The same 2bp deletion was identified in 3 patients with a mild form of generalised ichthyosis from 2 Algerian families. Casp14-/- mouse models had prominent dermatological features.
Sources: Expert Review
Mendeliome v0.1038 CLCNKA Zornitza Stark Gene: clcnka has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1034 CLCNKA Zornitza Stark Classified gene: CLCNKA as Amber List (moderate evidence)
Mendeliome v0.1034 CLCNKA Zornitza Stark Gene: clcnka has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1026 CLCNKA Zornitza Stark reviewed gene: CLCNKA: Rating: AMBER; Mode of pathogenicity: None; Publications: 18310267, 29254190; Phenotypes: Bartter syndrome, type 4b, digenic, OMIM #613090; Mode of inheritance: Other
Mendeliome v0.989 AGO1 Zornitza Stark gene: AGO1 was added
gene: AGO1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: AGO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AGO1 were set to 30213762; 22495306; 23020937; 25363768; 25356899; 27620904; 29346770; 28135719
Phenotypes for gene: AGO1 were set to Intellectual disability; autism
Review for gene: AGO1 was set to GREEN
Added comment: Multiple individuals reported with de novo variants in this gene, most as part of large ID cohorts so phenotypic information is scarce; however, given large number I have rated as Green.
Sources: Expert list
Mendeliome v0.975 IKZF5 Zornitza Stark gene: IKZF5 was added
gene: IKZF5 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: IKZF5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKZF5 were set to 31217188
Phenotypes for gene: IKZF5 were set to Thrombocytopaenia
Review for gene: IKZF5 was set to GREEN
Added comment: Five unrelated individuals with missense variants in this gene. Two de novo, three segregated with disease
Sources: Expert Review
Mendeliome v0.958 FUK Zornitza Stark Gene: fuk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.958 FUK Zornitza Stark Classified gene: FUK as Amber List (moderate evidence)
Mendeliome v0.958 FUK Zornitza Stark Gene: fuk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.957 FUK Zornitza Stark gene: FUK was added
gene: FUK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FUK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUK were set to 30503518
Phenotypes for gene: FUK were set to Congenital disorder of glycosylation with defective fucosylation 2, MIM# 618324
Review for gene: FUK was set to AMBER
Added comment: Two unrelated individuals reported.
Sources: Literature
Mendeliome v0.932 FAR1 Zornitza Stark Gene: far1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.929 FAR1 Zornitza Stark Classified gene: FAR1 as Amber List (moderate evidence)
Mendeliome v0.929 FAR1 Zornitza Stark Gene: far1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.928 FAR1 Zornitza Stark reviewed gene: FAR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25439727; Phenotypes: Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.928 EFHC1 Zornitza Stark Gene: efhc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.925 EFHC1 Zornitza Stark Classified gene: EFHC1 as Amber List (moderate evidence)
Mendeliome v0.925 EFHC1 Zornitza Stark Gene: efhc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.924 CEP89 Zornitza Stark Gene: cep89 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.921 CEP89 Zornitza Stark Classified gene: CEP89 as Amber List (moderate evidence)
Mendeliome v0.921 CEP89 Zornitza Stark Gene: cep89 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.916 RAB11A Zornitza Stark Gene: rab11a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.916 RAB11A Zornitza Stark Classified gene: RAB11A as Amber List (moderate evidence)
Mendeliome v0.916 RAB11A Zornitza Stark Gene: rab11a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.915 RAB11A Zornitza Stark Classified gene: RAB11A as Amber List (moderate evidence)
Mendeliome v0.915 RAB11A Zornitza Stark Gene: rab11a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.914 RAB11A Zornitza Stark gene: RAB11A was added
gene: RAB11A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAB11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB11A were set to 29100083
Phenotypes for gene: RAB11A were set to Intellectual disability; seizures
Review for gene: RAB11A was set to AMBER
Added comment: Five individuals reported with DNMs and neurodevelopmental phenotypes as part of this paper; however, clinical details are sparse. Emerging gene, phenotype not yet clearly delineated.
Sources: Literature
Mendeliome v0.913 RAB11B Zornitza Stark reviewed gene: RAB11B: Rating: AMBER; Mode of pathogenicity: None; Publications: 29100083; Phenotypes: Intellectual disability, seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.907 DDOST Zornitza Stark Gene: ddost has been classified as Amber List (Moderate Evidence).
Mendeliome v0.904 DDOST Zornitza Stark Classified gene: DDOST as Amber List (moderate evidence)
Mendeliome v0.904 DDOST Zornitza Stark Gene: ddost has been classified as Amber List (Moderate Evidence).
Mendeliome v0.903 DDOST Zornitza Stark reviewed gene: DDOST: Rating: AMBER; Mode of pathogenicity: None; Publications: 22305527; Phenotypes: Congenital disorder of glycosylation, type Ir, MIM# 614507; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.861 TP73 Alison Yeung Gene: tp73 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.861 TP73 Alison Yeung Classified gene: TP73 as Amber List (moderate evidence)
Mendeliome v0.861 TP73 Alison Yeung Gene: tp73 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.860 TP73 Alison Yeung gene: TP73 was added
gene: TP73 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TP73 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TP73 were set to PMID: 31130284
Phenotypes for gene: TP73 were set to Cortical malformation; Lissencephaly
Review for gene: TP73 was set to AMBER
Added comment: Two unrelated families reported. No functional data
Sources: Literature
Mendeliome v0.859 SMG8 Alison Yeung Gene: smg8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.859 SMG8 Alison Yeung Classified gene: SMG8 as Amber List (moderate evidence)
Mendeliome v0.859 SMG8 Alison Yeung Gene: smg8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.858 SMG8 Alison Yeung gene: SMG8 was added
gene: SMG8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SMG8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMG8 were set to PMID: 31130284
Phenotypes for gene: SMG8 were set to Intellectual disability
Review for gene: SMG8 was set to AMBER
Added comment: Two unrelated families reported. No functional data
Sources: Literature
Mendeliome v0.857 IQSEC3 Alison Yeung Gene: iqsec3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.857 IQSEC3 Alison Yeung Classified gene: IQSEC3 as Amber List (moderate evidence)
Mendeliome v0.857 IQSEC3 Alison Yeung Gene: iqsec3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.856 IQSEC3 Alison Yeung gene: IQSEC3 was added
gene: IQSEC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IQSEC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IQSEC3 were set to PMID: 31130284
Phenotypes for gene: IQSEC3 were set to Intellectual disability
Review for gene: IQSEC3 was set to AMBER
Added comment: Two unrelated families reported, no functional data
Sources: Literature
Mendeliome v0.855 ICE1 Alison Yeung Gene: ice1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.855 ICE1 Alison Yeung Classified gene: ICE1 as Amber List (moderate evidence)
Mendeliome v0.855 ICE1 Alison Yeung Gene: ice1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.854 ICE1 Alison Yeung gene: ICE1 was added
gene: ICE1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ICE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ICE1 were set to PMID: 31130284
Phenotypes for gene: ICE1 were set to Intellectual disability, cerebral atrophy
Review for gene: ICE1 was set to AMBER
Added comment: Two unrelated families reported, no functional data
Sources: Literature
Mendeliome v0.853 EIF2A Alison Yeung Gene: eif2a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.853 EIF2A Alison Yeung Classified gene: EIF2A as Amber List (moderate evidence)
Mendeliome v0.853 EIF2A Alison Yeung Gene: eif2a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.852 EIF2A Alison Yeung gene: EIF2A was added
gene: EIF2A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EIF2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF2A were set to PMID: 31130284
Phenotypes for gene: EIF2A were set to Intellectual disability, epilepsy
Review for gene: EIF2A was set to AMBER
Added comment: reported in two unrelated families
Sources: Literature
Mendeliome v0.843 CTNND2 Zornitza Stark Gene: ctnnd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.840 CTNND2 Zornitza Stark Classified gene: CTNND2 as Amber List (moderate evidence)
Mendeliome v0.840 CTNND2 Zornitza Stark Gene: ctnnd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.839 CTNND2 Zornitza Stark reviewed gene: CTNND2: Rating: AMBER; Mode of pathogenicity: None; Publications: 25839933, 29127138, 25807484; Phenotypes: Intellectual disability, Autism, Epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.829 LEMD2 Alison Yeung Gene: lemd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.829 LEMD2 Alison Yeung Classified gene: LEMD2 as Amber List (moderate evidence)
Mendeliome v0.829 LEMD2 Alison Yeung Gene: lemd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.829 LEMD2 Alison Yeung Classified gene: LEMD2 as Amber List (moderate evidence)
Mendeliome v0.829 LEMD2 Alison Yeung Gene: lemd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.828 LEMD2 Alison Yeung gene: LEMD2 was added
gene: LEMD2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LEMD2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LEMD2 were set to PMID: 30905398
Phenotypes for gene: LEMD2 were set to progeroid disorder
Review for gene: LEMD2 was set to AMBER
Added comment: two reported unrelated individuals, limited functional evidence
Sources: Literature
Mendeliome v0.827 PLD1 Zornitza Stark Gene: pld1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.823 PLD1 Zornitza Stark Classified gene: PLD1 as Amber List (moderate evidence)
Mendeliome v0.823 PLD1 Zornitza Stark Gene: pld1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.813 RIC1 Zornitza Stark Gene: ric1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.813 RIC1 Zornitza Stark Classified gene: RIC1 as Amber List (moderate evidence)
Mendeliome v0.813 RIC1 Zornitza Stark Gene: ric1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.812 RIC1 Zornitza Stark gene: RIC1 was added
gene: RIC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RIC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIC1 were set to 31932796
Phenotypes for gene: RIC1 were set to Cleft lip; cataract; tooth abnormality; intellectual disability; facial dysmorphism; ADHD
Review for gene: RIC1 was set to AMBER
Added comment: Zebrafish model and consanguineous families but homozygous-by-descent.
Sources: Literature
Mendeliome v0.802 SRGAP1 Zornitza Stark Gene: srgap1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.799 SRGAP1 Zornitza Stark Classified gene: SRGAP1 as Amber List (moderate evidence)
Mendeliome v0.799 SRGAP1 Zornitza Stark Gene: srgap1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.794 STN1 Zornitza Stark Gene: stn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.794 STN1 Zornitza Stark Classified gene: STN1 as Amber List (moderate evidence)
Mendeliome v0.794 STN1 Zornitza Stark Gene: stn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.793 STN1 Zornitza Stark gene: STN1 was added
gene: STN1 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: STN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STN1 were set to 27432940
Phenotypes for gene: STN1 were set to Cerebroretinal microangiopathy with calcification and cysts 2, MIM#617341
Review for gene: STN1 was set to AMBER
Added comment: Two unrelated individuals reported.
Sources: Expert list
Mendeliome v0.788 TDP2 Zornitza Stark gene: TDP2 was added
gene: TDP2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: TDP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TDP2 were set to 31410782; 30109272; 24658003
Phenotypes for gene: TDP2 were set to Spinocerebellar ataxia, autosomal recessive 23; OMIM #616949
Review for gene: TDP2 was set to GREEN
Added comment: ID is part of the phenotype: 4 families with 6 affected patients, with functional evidence.

1 family with 3 affected sibs with homozygous splice site mutation in the TDP2 gene. Patient cell extracts showed absence of the full-length TDP2 protein and absence of 5-prime TDP activity, consistent with a loss of function, although 3-prime TDP activity, conferred by TDP1, was normal. In addition, patient lymphoblastoid cells were hypersensitive to the TOP2 poison etoposide. The findings indicated impaired capacity for double-strand break repair.

1 unrelated Egyptian patient with a similar disorder was homozygous for a truncating mutation in the TDP2 gene

1 unrelated Caucasian patient with same homozygous splice site mutation in the TDP2 gene. Western blot analysis did not detect TDP2 protein in patient primary skin fibroblasts. Patient fibroblasts showed an inability to rapidly repair topoisomerase-induced DNA double-strand breaks in the nucleus and also showed a profound hypersensitivity to this type of DNA damage. Complementation of patient cells with recombinant human TDP2 restored normal rates of nuclear DSB repair.
Sources: Expert list
Mendeliome v0.785 SLC35A3 Zornitza Stark Gene: slc35a3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.782 SLC35A3 Zornitza Stark Classified gene: SLC35A3 as Amber List (moderate evidence)
Mendeliome v0.782 SLC35A3 Zornitza Stark Gene: slc35a3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.781 SLC9A7 Zornitza Stark Gene: slc9a7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.781 SLC9A7 Zornitza Stark Classified gene: SLC9A7 as Amber List (moderate evidence)
Mendeliome v0.781 SLC9A7 Zornitza Stark Gene: slc9a7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.780 SLC9A7 Zornitza Stark gene: SLC9A7 was added
gene: SLC9A7 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: SLC9A7 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SLC9A7 were set to 30335141
Phenotypes for gene: SLC9A7 were set to Intellectual developmental disorder, X-linked 108; OMIM #301024
Review for gene: SLC9A7 was set to AMBER
Added comment: 6 males from 2 unrelated families with hemizygous missense mutation in the SLC9A7 gene. The mutation segregated with the disorder in the family. In vitro functional expression studies in CHO cells (AP-1 cells) showed that the mutation caused decreased levels of protein expression and reduced oligosaccharide maturation/glycosylation compared to wildtype, indicating impaired posttranslational processing. Subcellular localization studies indicated that protein trafficking was unaffected by the mutation. However, examination of the trans-Golgi compartment suggested a gain-of-function effect and a perturbation of glycosylation of secretory cargo. Serum transferrin studies in 1 patient suggested a glycosylation defect.
Sources: Literature
Mendeliome v0.777 ZC3H14 Zornitza Stark Gene: zc3h14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.775 ZC3H14 Zornitza Stark Classified gene: ZC3H14 as Amber List (moderate evidence)
Mendeliome v0.775 ZC3H14 Zornitza Stark Gene: zc3h14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.774 ZFHX3 Zornitza Stark Gene: zfhx3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.774 ZFHX3 Zornitza Stark Classified gene: ZFHX3 as Amber List (moderate evidence)
Mendeliome v0.774 ZFHX3 Zornitza Stark Gene: zfhx3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.770 MDH1 Zornitza Stark Gene: mdh1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.770 MDH1 Zornitza Stark Classified gene: MDH1 as Amber List (moderate evidence)
Mendeliome v0.770 MDH1 Zornitza Stark Gene: mdh1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.769 MDH1 Zornitza Stark gene: MDH1 was added
gene: MDH1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: MDH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDH1 were set to 31538237
Phenotypes for gene: MDH1 were set to epilepsy; microcephaly; intellectual disability
Review for gene: MDH1 was set to AMBER
Added comment: single consanguinous family with biallelic missense variant in this gene and epilepsy, microcephaly, ID; some functional data.
Sources: Literature
Mendeliome v0.768 ISLR2 Zornitza Stark Gene: islr2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.768 ISLR2 Zornitza Stark Classified gene: ISLR2 as Amber List (moderate evidence)
Mendeliome v0.768 ISLR2 Zornitza Stark Gene: islr2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.767 ISLR2 Zornitza Stark gene: ISLR2 was added
gene: ISLR2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: ISLR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ISLR2 were set to 30483960
Phenotypes for gene: ISLR2 were set to hydrocephalus; arthrogryposis; abdominal distension
Review for gene: ISLR2 was set to AMBER
Added comment: single consanguineous family with hydrocephalus and arthrogryposis and homozygous truncating variant, mouse model has hydrocephalus
Sources: Literature
Mendeliome v0.755 NSMCE3 Zornitza Stark Gene: nsmce3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.752 NSMCE3 Zornitza Stark Classified gene: NSMCE3 as Amber List (moderate evidence)
Mendeliome v0.752 NSMCE3 Zornitza Stark Gene: nsmce3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.751 NSMCE3 Zornitza Stark reviewed gene: NSMCE3: Rating: AMBER; Mode of pathogenicity: None; Publications: 27427983; Phenotypes: Lung disease, immunodeficiency, and chromosome breakage syndrome, MIM#617241; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.750 MYSM1 Zornitza Stark gene: MYSM1 was added
gene: MYSM1 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: MYSM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYSM1 were set to 4288411; 28115216; 26220525
Phenotypes for gene: MYSM1 were set to Bone marrow failure syndrome 4, MIM#618116
Review for gene: MYSM1 was set to GREEN
Added comment: early-onset anaemia, leukopaenia, and decreased B cells, may have thrombocytopaenia or variable additional non-haematologic features, such as facial dysmorphism, skeletal anomalies, and mild developmental delay
Sources: Expert list
Mendeliome v0.747 IRF3 Zornitza Stark Gene: irf3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.744 IRF3 Zornitza Stark Classified gene: IRF3 as Amber List (moderate evidence)
Mendeliome v0.744 IRF3 Zornitza Stark Gene: irf3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.743 IRF3 Zornitza Stark reviewed gene: IRF3: Rating: AMBER; Mode of pathogenicity: None; Publications: 26513235; Phenotypes: {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 7}, MIM# 616532; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.733 ANLN Zornitza Stark Classified gene: ANLN as Amber List (moderate evidence)
Mendeliome v0.733 ANLN Zornitza Stark Gene: anln has been classified as Amber List (Moderate Evidence).
Mendeliome v0.732 ANLN Zornitza Stark reviewed gene: ANLN: Rating: AMBER; Mode of pathogenicity: None; Publications: 24676636, 30002222; Phenotypes: Focal segmental glomerulosclerosis 8, OMIM #616032; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.728 CD2AP Zornitza Stark Gene: cd2ap has been classified as Amber List (Moderate Evidence).
Mendeliome v0.725 CD2AP Zornitza Stark Classified gene: CD2AP as Amber List (moderate evidence)
Mendeliome v0.725 CD2AP Zornitza Stark Gene: cd2ap has been classified as Amber List (Moderate Evidence).
Mendeliome v0.724 CD2AP Zornitza Stark reviewed gene: CD2AP: Rating: AMBER; Mode of pathogenicity: None; Publications: 30612599, 17713465; Phenotypes: Glomerulosclerosis, focal segmental, 3, OMIM #607832; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.722 LAMA5 Zornitza Stark Gene: lama5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.722 LAMA5 Zornitza Stark Classified gene: LAMA5 as Amber List (moderate evidence)
Mendeliome v0.722 LAMA5 Zornitza Stark Gene: lama5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.702 ALKBH8 Zornitza Stark Classified gene: ALKBH8 as Amber List (moderate evidence)
Mendeliome v0.702 ALKBH8 Zornitza Stark Gene: alkbh8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.684 TRIM28 Zornitza Stark gene: TRIM28 was added
gene: TRIM28 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: TRIM28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM28 were set to 30694527
Phenotypes for gene: TRIM28 were set to Wilm's tumour
Review for gene: TRIM28 was set to GREEN
Added comment: Eleven individuals with germline variants identified; plus one somatic. Exome sequencing on eight tumor DNA samples from six individuals showed loss-of-heterozygosity (LOH) of the TRIM28-locus by mitotic recombination in seven tumors, suggesting that TRIM28 functions as a tumor suppressor gene in Wilms tumor development.
Sources: Literature
Mendeliome v0.680 DEF6 Zornitza Stark Gene: def6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.680 DEF6 Zornitza Stark Classified gene: DEF6 as Amber List (moderate evidence)
Mendeliome v0.680 DEF6 Zornitza Stark Gene: def6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.679 DEF6 Zornitza Stark gene: DEF6 was added
gene: DEF6 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: DEF6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DEF6 were set to 31308374
Phenotypes for gene: DEF6 were set to Systemic autoimmunity
Review for gene: DEF6 was set to AMBER
Added comment: Three individuals from two families, some functional data.
Sources: Literature
Mendeliome v0.671 C19orf70 Zornitza Stark gene: C19orf70 was added
gene: C19orf70 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: C19orf70 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C19orf70 were set to 29618761; 27623147; 27485409
Phenotypes for gene: C19orf70 were set to Combined oxidative phosphorylation deficiency 37, MIM# 618329
Review for gene: C19orf70 was set to GREEN
Added comment: Three unrelated families reported. HGNC approved name MICOS13.
Sources: Expert list
Mendeliome v0.669 MIPEP Zornitza Stark gene: MIPEP was added
gene: MIPEP was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: MIPEP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MIPEP were set to 27799064
Phenotypes for gene: MIPEP were set to Combined oxidative phosphorylation deficiency 31, MIM# 617228
Review for gene: MIPEP was set to GREEN
Added comment: Four unrelated children reported.
Sources: Expert list
Mendeliome v0.668 MRPS14 Zornitza Stark gene: MRPS14 was added
gene: MRPS14 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: MRPS14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPS14 were set to 30358850
Phenotypes for gene: MRPS14 were set to Combined oxidative phosphorylation deficiency 38, MIM# 618378
Review for gene: MRPS14 was set to RED
Added comment: Single individual reported, functional data.
Sources: Expert list
Mendeliome v0.653 H3F3B Zornitza Stark Classified gene: H3F3B as Amber List (moderate evidence)
Mendeliome v0.653 H3F3B Zornitza Stark Gene: h3f3b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.652 H3F3A Zornitza Stark Gene: h3f3a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.652 H3F3A Zornitza Stark Classified gene: H3F3A as Amber List (moderate evidence)
Mendeliome v0.652 H3F3A Zornitza Stark Gene: h3f3a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.643 RUSC2 Zornitza Stark Gene: rusc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.640 RUSC2 Zornitza Stark Classified gene: RUSC2 as Amber List (moderate evidence)
Mendeliome v0.640 RUSC2 Zornitza Stark Gene: rusc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.639 RUSC2 Zornitza Stark reviewed gene: RUSC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27612186; Phenotypes: Mental retardation, autosomal recessive 61, MIM# 617773; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.639 RSRC1 Zornitza Stark Gene: rsrc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.639 RSRC1 Zornitza Stark Classified gene: RSRC1 as Amber List (moderate evidence)
Mendeliome v0.639 RSRC1 Zornitza Stark Gene: rsrc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.638 RSRC1 Zornitza Stark gene: RSRC1 was added
gene: RSRC1 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: RSRC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RSRC1 were set to 28640246; 29522154
Phenotypes for gene: RSRC1 were set to Intellectual developmental disorder, autosomal recessive 70, MIM# 618402
Review for gene: RSRC1 was set to AMBER
Added comment: Two unrelated families reported, 8 affected individuals.
Sources: Expert list
Mendeliome v0.634 USP27X Zornitza Stark Gene: usp27x has been classified as Amber List (Moderate Evidence).
Mendeliome v0.634 USP27X Zornitza Stark Classified gene: USP27X as Amber List (moderate evidence)
Mendeliome v0.634 USP27X Zornitza Stark Gene: usp27x has been classified as Amber List (Moderate Evidence).
Mendeliome v0.633 USP27X Zornitza Stark gene: USP27X was added
gene: USP27X was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: USP27X was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: USP27X were set to 25644381
Phenotypes for gene: USP27X were set to Mental retardation, X-linked 105, MIM#300984
Review for gene: USP27X was set to AMBER
Added comment: Four individuals from two unrelated families reported.
Sources: Expert list
Mendeliome v0.632 KLHL15 Zornitza Stark Gene: klhl15 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.632 KLHL15 Zornitza Stark Classified gene: KLHL15 as Amber List (moderate evidence)
Mendeliome v0.632 KLHL15 Zornitza Stark Gene: klhl15 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.631 KLHL15 Zornitza Stark gene: KLHL15 was added
gene: KLHL15 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: KLHL15 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: KLHL15 were set to 25644381; 24817631
Phenotypes for gene: KLHL15 were set to Mental retardation, X-linked 103, MIM#300982
Review for gene: KLHL15 was set to AMBER
Added comment: Two families described: variants maternally inherited in both, one deletion, the other truncating.
Sources: Literature
Mendeliome v0.611 PIGP Zornitza Stark Gene: pigp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.611 PIGP Zornitza Stark Classified gene: PIGP as Amber List (moderate evidence)
Mendeliome v0.611 PIGP Zornitza Stark Gene: pigp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.610 PIGP Zornitza Stark gene: PIGP was added
gene: PIGP was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: PIGP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGP were set to 31139695
Phenotypes for gene: PIGP were set to Epileptic encephalopathy, early infantile, 55, MIM# 617599
Review for gene: PIGP was set to AMBER
Added comment: Three individuals from two unrelated families reported.
Sources: Expert list
Mendeliome v0.605 GLIS2 Zornitza Stark Gene: glis2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.601 GLIS2 Zornitza Stark Classified gene: GLIS2 as Amber List (moderate evidence)
Mendeliome v0.601 GLIS2 Zornitza Stark Gene: glis2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.600 GLIS2 Zornitza Stark reviewed gene: GLIS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 17618285, 23559409; Phenotypes: Nephronophthisis 7, OMIM#611498; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.596 IFT74 Zornitza Stark Gene: ift74 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.596 IFT74 Zornitza Stark Classified gene: IFT74 as Amber List (moderate evidence)
Mendeliome v0.596 IFT74 Zornitza Stark Gene: ift74 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.595 IFT74 Zornitza Stark gene: IFT74 was added
gene: IFT74 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: IFT74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT74 were set to 27486776
Phenotypes for gene: IFT74 were set to Bardet-Biedl syndrome 20, MIM# 617119
Review for gene: IFT74 was set to AMBER
Added comment: Single family and functional data.
Sources: Expert list
Mendeliome v0.589 IFT81 Zornitza Stark Classified gene: IFT81 as Amber List (moderate evidence)
Mendeliome v0.589 IFT81 Zornitza Stark Gene: ift81 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.588 IFT81 Zornitza Stark reviewed gene: IFT81: Rating: AMBER; Mode of pathogenicity: None; Publications: 27666822; Phenotypes: Short-rib thoracic dysplasia 19 with or without polydactyly, MIM# 617895; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.588 PDE6D Zornitza Stark Gene: pde6d has been classified as Amber List (Moderate Evidence).
Mendeliome v0.586 PDE6D Zornitza Stark Classified gene: PDE6D as Amber List (moderate evidence)
Mendeliome v0.586 PDE6D Zornitza Stark Gene: pde6d has been classified as Amber List (Moderate Evidence).
Mendeliome v0.565 ADAM22 Zornitza Stark gene: ADAM22 was added
gene: ADAM22 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: ADAM22 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAM22 were set to 27066583; 30237576
Phenotypes for gene: ADAM22 were set to Epileptic encephalopathy, early infantile, 61, MIM# 617933
Review for gene: ADAM22 was set to AMBER
Added comment: Two families reported; the second one as part of a large consanguineous cohort.
Sources: Expert list
Mendeliome v0.541 NADSYN1 Zornitza Stark gene: NADSYN1 was added
gene: NADSYN1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: NADSYN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NADSYN1 were set to 31883644
Phenotypes for gene: NADSYN1 were set to Multiple congenital abnormalities; absent kidneys; cardiac; limb; vertebral
Review for gene: NADSYN1 was set to GREEN
Added comment: Five individuals from four unrelated families.
Sources: Literature
Mendeliome v0.535 SPATC1L Zornitza Stark Gene: spatc1l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.535 SPATC1L Zornitza Stark Classified gene: SPATC1L as Amber List (moderate evidence)
Mendeliome v0.535 SPATC1L Zornitza Stark Gene: spatc1l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.534 SPATC1L Zornitza Stark gene: SPATC1L was added
gene: SPATC1L was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: SPATC1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATC1L were set to 30177775
Phenotypes for gene: SPATC1L were set to Deafness
Review for gene: SPATC1L was set to AMBER
Added comment: Two families with compound het variants, and one family with heterozygous variant and dominant pattern of hearing loss described, some functional data.
Sources: Expert list
Mendeliome v0.533 WBP2 Zornitza Stark Gene: wbp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.533 WBP2 Zornitza Stark Classified gene: WBP2 as Amber List (moderate evidence)
Mendeliome v0.533 WBP2 Zornitza Stark Gene: wbp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.532 WBP2 Zornitza Stark gene: WBP2 was added
gene: WBP2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: WBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WBP2 were set to 26881968
Phenotypes for gene: WBP2 were set to Deafness, autosomal recessive 107, MIM# 617639
Review for gene: WBP2 was set to AMBER
Added comment: Two unrelated families identified in a large cohort; supportive animal model data.
Sources: Expert list
Mendeliome v0.531 TMEM132E Zornitza Stark Gene: tmem132e has been classified as Amber List (Moderate Evidence).
Mendeliome v0.531 TMEM132E Zornitza Stark Classified gene: TMEM132E as Amber List (moderate evidence)
Mendeliome v0.531 TMEM132E Zornitza Stark Gene: tmem132e has been classified as Amber List (Moderate Evidence).
Mendeliome v0.530 TMEM132E Zornitza Stark gene: TMEM132E was added
gene: TMEM132E was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: TMEM132E was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM132E were set to 25331638
Phenotypes for gene: TMEM132E were set to Deafness, autosomal recessive 99, MIM# 618481
Review for gene: TMEM132E was set to AMBER
Added comment: Single family reported, supportive animal model.
Sources: Expert list
Mendeliome v0.528 SPNS2 Zornitza Stark Gene: spns2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.528 SPNS2 Zornitza Stark Classified gene: SPNS2 as Amber List (moderate evidence)
Mendeliome v0.528 SPNS2 Zornitza Stark Gene: spns2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.527 SPNS2 Zornitza Stark gene: SPNS2 was added
gene: SPNS2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: SPNS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPNS2 were set to 25356849
Phenotypes for gene: SPNS2 were set to Deafness, autosomal recessive 115, MIM# 618457
Review for gene: SPNS2 was set to AMBER
Added comment: Single family reported, mouse model shows progressive hearing loss.
Sources: Expert list
Mendeliome v0.526 ESRP1 Zornitza Stark Gene: esrp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.526 ESRP1 Zornitza Stark Classified gene: ESRP1 as Amber List (moderate evidence)
Mendeliome v0.526 ESRP1 Zornitza Stark Gene: esrp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.525 ESRP1 Zornitza Stark gene: ESRP1 was added
gene: ESRP1 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: ESRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESRP1 were set to 29107558
Phenotypes for gene: ESRP1 were set to Deafness, autosomal recessive 109, MIM# 618013
Review for gene: ESRP1 was set to AMBER
Added comment: Single family with affected sibs, mouse model.
Sources: Expert list
Mendeliome v0.520 PPIP5K2 Zornitza Stark Gene: ppip5k2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.520 PPIP5K2 Zornitza Stark Classified gene: PPIP5K2 as Amber List (moderate evidence)
Mendeliome v0.520 PPIP5K2 Zornitza Stark Gene: ppip5k2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.519 PPIP5K2 Zornitza Stark gene: PPIP5K2 was added
gene: PPIP5K2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: PPIP5K2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPIP5K2 were set to 29590114
Phenotypes for gene: PPIP5K2 were set to Deafness, autosomal recessive 100, MIM# 618422
Review for gene: PPIP5K2 was set to AMBER
Added comment: Two apparently unrelated families with multiple affecteds segregating a homozygous missense variant; mouse model.
Sources: Expert list
Mendeliome v0.518 ROR1 Zornitza Stark Gene: ror1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.518 ROR1 Zornitza Stark Classified gene: ROR1 as Amber List (moderate evidence)
Mendeliome v0.518 ROR1 Zornitza Stark Gene: ror1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.517 ROR1 Zornitza Stark gene: ROR1 was added
gene: ROR1 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: ROR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ROR1 were set to 27162350
Phenotypes for gene: ROR1 were set to Deafness, autosomal recessive 108, MIM# 617654
Review for gene: ROR1 was set to AMBER
Added comment: Single family, sibs with homozygous missense variant; mouse model.
Sources: Expert list
Mendeliome v0.516 RIPOR2 Zornitza Stark Gene: ripor2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.516 RIPOR2 Zornitza Stark Classified gene: RIPOR2 as Amber List (moderate evidence)
Mendeliome v0.516 RIPOR2 Zornitza Stark Gene: ripor2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.515 RIPOR2 Zornitza Stark gene: RIPOR2 was added
gene: RIPOR2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: RIPOR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIPOR2 were set to 24958875
Phenotypes for gene: RIPOR2 were set to Deafness, autosomal recessive 104, MIM# 616515
Review for gene: RIPOR2 was set to AMBER
Added comment: Single family and animal model data.
Sources: Expert list
Mendeliome v0.514 PROC Zornitza Stark Phenotypes for gene: PROC were changed from to Thrombophilia due to protein C deficiency, autosomal dominant (176860); Thrombophilia due to protein C deficiency, autosomal recessive (612304)
Mendeliome v0.512 PROC Chris Richmond reviewed gene: PROC: Rating: GREEN; Mode of pathogenicity: None; Publications: 22545135, 30925296; Phenotypes: Thrombophilia due to protein C deficiency, autosomal dominant (176860), Thrombophilia due to protein C deficiency, autosomal recessive (612304); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.512 CLDN9 Zornitza Stark Gene: cldn9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.512 CLDN9 Zornitza Stark Classified gene: CLDN9 as Amber List (moderate evidence)
Mendeliome v0.512 CLDN9 Zornitza Stark Gene: cldn9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.511 CLDN9 Zornitza Stark gene: CLDN9 was added
gene: CLDN9 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: CLDN9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLDN9 were set to 31175426; 19696885
Phenotypes for gene: CLDN9 were set to Deafness, autosomal recessive
Review for gene: CLDN9 was set to AMBER
Added comment: Single family with multiple sibs reported; mouse model exhibits deafness.
Sources: Literature
Mendeliome v0.510 TOP2B Zornitza Stark Gene: top2b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.510 TOP2B Zornitza Stark Classified gene: TOP2B as Amber List (moderate evidence)
Mendeliome v0.510 TOP2B Zornitza Stark Gene: top2b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.509 TOP2B Zornitza Stark gene: TOP2B was added
gene: TOP2B was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: TOP2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TOP2B were set to 31198993
Phenotypes for gene: TOP2B were set to Autosomal dominant deafness
Review for gene: TOP2B was set to AMBER
Added comment: One multigenerational family where variant in this gene segregated; two additional variants identified in a cohort; supportive animal model data.
Sources: Literature
Mendeliome v0.495 CLIC5 Zornitza Stark Classified gene: CLIC5 as Amber List (moderate evidence)
Mendeliome v0.495 CLIC5 Zornitza Stark Gene: clic5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.494 CLIC5 Zornitza Stark reviewed gene: CLIC5: Rating: AMBER; Mode of pathogenicity: None; Publications: 24781754, 17021174; Phenotypes: Deafness, autosomal recessive 103, MIM# 616042; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.484 ELMOD3 Zornitza Stark Gene: elmod3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.481 ELMOD3 Zornitza Stark Classified gene: ELMOD3 as Amber List (moderate evidence)
Mendeliome v0.481 ELMOD3 Zornitza Stark Gene: elmod3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.480 ELMOD3 Zornitza Stark reviewed gene: ELMOD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 24039609, 31628468, 30284680, 29713870; Phenotypes: Deafness, autosomal recessive 88, MIM# 615429, Deafness, autosomal dominant; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.478 GRXCR2 Zornitza Stark Gene: grxcr2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.476 GRXCR2 Zornitza Stark Classified gene: GRXCR2 as Amber List (moderate evidence)
Mendeliome v0.476 GRXCR2 Zornitza Stark Gene: grxcr2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.475 GRXCR2 Zornitza Stark reviewed gene: GRXCR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24619944; Phenotypes: Deafness, autosomal recessive 101, MIM# 615837; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.473 KITLG Zornitza Stark Gene: kitlg has been classified as Amber List (Moderate Evidence).
Mendeliome v0.470 KITLG Zornitza Stark Classified gene: KITLG as Amber List (moderate evidence)
Mendeliome v0.470 KITLG Zornitza Stark Gene: kitlg has been classified as Amber List (Moderate Evidence).
Mendeliome v0.469 KITLG Zornitza Stark reviewed gene: KITLG: Rating: AMBER; Mode of pathogenicity: None; Publications: 26522471; Phenotypes: Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.466 MIR96 Zornitza Stark Classified gene: MIR96 as Amber List (moderate evidence)
Mendeliome v0.466 MIR96 Zornitza Stark Gene: mir96 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.465 MIR96 Zornitza Stark reviewed gene: MIR96: Rating: AMBER; Mode of pathogenicity: None; Publications: 19363479, 29325119; Phenotypes: Deafness, autosomal dominant 50, MIM# 613074; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.465 NUP188 Zornitza Stark Gene: nup188 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.462 NUP188 Zornitza Stark Classified gene: NUP188 as Amber List (moderate evidence)
Mendeliome v0.462 NUP188 Zornitza Stark Gene: nup188 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.461 NUP188 Zornitza Stark reviewed gene: NUP188: Rating: AMBER; Mode of pathogenicity: None; Publications: https://doi.org/10.1159/000504818, 28726809; Phenotypes: microcephaly, ID, cataract; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.455 ATP2B3 Zornitza Stark Gene: atp2b3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.452 ATP2B3 Zornitza Stark Classified gene: ATP2B3 as Amber List (moderate evidence)
Mendeliome v0.452 ATP2B3 Zornitza Stark Gene: atp2b3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.451 ATP2B3 Zornitza Stark reviewed gene: ATP2B3: Rating: AMBER; Mode of pathogenicity: None; Publications: 22912398, 27653636, 27632770; Phenotypes: Spinocerebellar ataxia, X-linked 1, MIM#302500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.451 CACNB4 Zornitza Stark Gene: cacnb4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.449 CACNB4 Zornitza Stark Classified gene: CACNB4 as Amber List (moderate evidence)
Mendeliome v0.449 CACNB4 Zornitza Stark Gene: cacnb4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.447 CACNB4 Zornitza Stark reviewed gene: CACNB4: Rating: AMBER; Mode of pathogenicity: None; Publications: 10762541, 9628818, 27003325; Phenotypes: Episodic ataxia, type 5, MIM#613855; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.438 CCDC88C Zornitza Stark Gene: ccdc88c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.435 CCDC88C Zornitza Stark Classified gene: CCDC88C as Amber List (moderate evidence)
Mendeliome v0.435 CCDC88C Zornitza Stark Gene: ccdc88c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.434 CCDC88C Zornitza Stark reviewed gene: CCDC88C: Rating: AMBER; Mode of pathogenicity: None; Publications: 25062847, 30398676; Phenotypes: Spinocerebellar ataxia 40, MIM#616053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.426 FAT2 Zornitza Stark Gene: fat2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.426 FAT2 Zornitza Stark Classified gene: FAT2 as Amber List (moderate evidence)
Mendeliome v0.426 FAT2 Zornitza Stark Gene: fat2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.425 FAT2 Zornitza Stark gene: FAT2 was added
gene: FAT2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: FAT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FAT2 were set to 29053796
Phenotypes for gene: FAT2 were set to Spinocerebellar ataxia 45, MIM#617769
Review for gene: FAT2 was set to AMBER
Added comment: Segregates in one family, and identified in one apparently sporadic case. In vitro functional evidence.
Sources: Expert list
Mendeliome v0.422 MN1 Zornitza Stark Phenotypes for gene: MN1 were changed from to Intellectual disability; dysmophic features; rhombencephalosynapsis
Mendeliome v0.418 MN1 Zornitza Stark reviewed gene: MN1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31834374, 31839203; Phenotypes: Intellectual disability, dysmophic features, rhombencephalosynapsis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.416 EEF1B2 Zornitza Stark Gene: eef1b2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.416 EEF1B2 Zornitza Stark Classified gene: EEF1B2 as Amber List (moderate evidence)
Mendeliome v0.416 EEF1B2 Zornitza Stark Gene: eef1b2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.415 EEF1B2 Zornitza Stark gene: EEF1B2 was added
gene: EEF1B2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: EEF1B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEF1B2 were set to 31845318; 21937992
Phenotypes for gene: EEF1B2 were set to Intellectual disability
Review for gene: EEF1B2 was set to AMBER
Added comment: 5 individuals from two unrelated families described in the literature so far, no functional data but gene belongs to a family implicated in neurodevelopmental disorders.
Sources: Literature
Mendeliome v0.398 NLRP2 Zornitza Stark Phenotypes for gene: NLRP2 were changed from to female infertility; early embryonic arrest
Mendeliome v0.395 NLRP2 Belinda Chong reviewed gene: NLRP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30877238; Phenotypes: female infertility, early embryonic arrest; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.382 XPO5 Zornitza Stark Gene: xpo5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.379 XPO5 Zornitza Stark Classified gene: XPO5 as Amber List (moderate evidence)
Mendeliome v0.379 XPO5 Zornitza Stark Gene: xpo5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.378 XPO5 Zornitza Stark reviewed gene: XPO5: Rating: AMBER; Mode of pathogenicity: None; Publications: 26878725; Phenotypes: Nephrotic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.374 KANK1 Zornitza Stark Classified gene: KANK1 as Amber List (moderate evidence)
Mendeliome v0.374 KANK1 Zornitza Stark Added comment: Comment on list classification: Amber for nephrotic after discussion with Chirag Patel.
Mendeliome v0.374 KANK1 Zornitza Stark Gene: kank1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.373 KANK4 Zornitza Stark Gene: kank4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.373 KANK4 Zornitza Stark Classified gene: KANK4 as Amber List (moderate evidence)
Mendeliome v0.373 KANK4 Zornitza Stark Gene: kank4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.372 KANK4 Zornitza Stark gene: KANK4 was added
gene: KANK4 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: KANK4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KANK4 were set to 25961457
Phenotypes for gene: KANK4 were set to Nephrotic syndrome
Review for gene: KANK4 was set to AMBER
Added comment: Two individuals from a single family reported; gene belongs to a family implicated in nephrotic syndrome.
Sources: Expert list
Mendeliome v0.370 KCNT2 Zornitza Stark gene: KCNT2 was added
gene: KCNT2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: KCNT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNT2 were set to 29069600; 29740868
Phenotypes for gene: KCNT2 were set to Epileptic encephalopathy, early infantile, 57, MIM#617771; Developmental and epileptic encephalopathy
Review for gene: KCNT2 was set to GREEN
Added comment: Reviewed by E Palmer: Ambrosino et al described 2 unrelated females with de novo variants in KCNT2. The first patient had the variant p.(Arg190His) had with West syndrome followed by Lennox-Gastaut syndrome , the second patient had the variant p.(Arg190Pro) and DEE with migrating focal seizures. Both variants were absent gnomad and had supportive in silico support for pathogenicity. In an electrophisological model both KCNT2 R190P and KCNT2 R190H increased maximal current density and shifted toward more negative membrane potential values the activation curve of KCNT2 channels, consistent with gain of function effects. PMID: 29740868.

Gururaj et al describe one male with de novo variant in KCNT2 p. (Phe240Leu) and early infantile epileptic encephalopathy. he variant was absent gnomad and supportive evidence of pathogenicity This variant was electrophysiologically modelled and revealed that the variant resulted in a 'change in function' demonstrating unusual altered selectivity in KNa channels.PMID: 29069600.
Sources: Literature
Mendeliome v0.364 GDF11 Zornitza Stark Gene: gdf11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.364 GDF11 Zornitza Stark Classified gene: GDF11 as Amber List (moderate evidence)
Mendeliome v0.364 GDF11 Zornitza Stark Gene: gdf11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.363 GDF11 Zornitza Stark gene: GDF11 was added
gene: GDF11 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: GDF11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GDF11 were set to 31215115
Phenotypes for gene: GDF11 were set to Cleft lip and palate
Review for gene: GDF11 was set to AMBER
Added comment: Cleft lip and palate, and rib and vertebral hypersegmentation in a single family. Mouse model.
Sources: Literature
Mendeliome v0.359 MICB Sebastian Lunke changed review comment from: This gene is included in a large number of publications as it plays an central role immunity (MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I CHAIN-RELATED GENE B). However beyond a number of susceptibility associations, it does not appear to have been firmly associated with disease in patients.; to: This gene is included in a large number of publications as it plays an central role immunity (MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I CHAIN-RELATED GENE B). However beyond a number of susceptibility associations, it does not appear to have been firmly associated with disease in patients.

https://ghr.nlm.nih.gov/gene/MICB#resources
Mendeliome v0.359 PPP1R12A Zornitza Stark reviewed gene: PPP1R12A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual disability, holoprosencephaly, disorder of sex development; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.359 ANKRD17 Zornitza Stark Gene: ankrd17 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.358 ANKRD17 Zornitza Stark Classified gene: ANKRD17 as Amber List (moderate evidence)
Mendeliome v0.358 ANKRD17 Zornitza Stark Gene: ankrd17 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.357 ANKRD17 Zornitza Stark reviewed gene: ANKRD17: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual disability, dysmorphic features; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.347 SLC12A2 Zornitza Stark Gene: slc12a2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.347 SLC12A2 Zornitza Stark Classified gene: SLC12A2 as Amber List (moderate evidence)
Mendeliome v0.347 SLC12A2 Zornitza Stark Gene: slc12a2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.346 SLC12A2 Zornitza Stark gene: SLC12A2 was added
gene: SLC12A2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: SLC12A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC12A2 were set to 30740830
Phenotypes for gene: SLC12A2 were set to Kilquist syndrome; deafness; intellectual disability; dysmorphic features; absent salivation
Review for gene: SLC12A2 was set to AMBER
Added comment: Single individual with bi-alllelic deletion described; mouse model recapitulated the phenotype.
Sources: Literature
Mendeliome v0.345 PANK4 Zornitza Stark Gene: pank4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.345 PANK4 Zornitza Stark Classified gene: PANK4 as Amber List (moderate evidence)
Mendeliome v0.345 PANK4 Zornitza Stark Gene: pank4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.344 PANK4 Zornitza Stark gene: PANK4 was added
gene: PANK4 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: PANK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PANK4 were set to 30585370
Phenotypes for gene: PANK4 were set to Congenital posterior cataract
Review for gene: PANK4 was set to AMBER
Added comment: Variant segregated with cataract in single 4-generation family, functional data including mouse model.
Sources: Literature
Mendeliome v0.327 TARS Zornitza Stark Gene: tars has been classified as Amber List (Moderate Evidence).
Mendeliome v0.327 TARS Zornitza Stark Classified gene: TARS as Amber List (moderate evidence)
Mendeliome v0.327 TARS Zornitza Stark Gene: tars has been classified as Amber List (Moderate Evidence).
Mendeliome v0.326 TARS Zornitza Stark gene: TARS was added
gene: TARS was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: TARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TARS were set to 31374204
Phenotypes for gene: TARS were set to Trichothiodystrophy 7, nonphotosensitive; OMIM #618546
Review for gene: TARS was set to AMBER
Added comment: Clinical features of trichothiodystrophy (TTD) include ichthyosis, intellectual disability, decreased fertility, short stature.

2 unrelated patients with non-photosensitive-TTD, in whom limited clinical information was available (one with DD): one compound heterozygous TARS variants, second homozygous for TARS variant. They showed that the variants had a profound effect on TARS protein stability and enzymatic function.
Sources: Literature
Mendeliome v0.288 MAST1 Zornitza Stark gene: MAST1 was added
gene: MAST1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: MAST1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST1 were set to 31721002; 30449657
Phenotypes for gene: MAST1 were set to Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations; OMIM #618273
Review for gene: MAST1 was set to GREEN
Added comment: 6 unrelated patients with mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (MCCCHCM) with de novo heterozygous mutations in MAST1 gene. In vitro functional studies showed that 1 of the variants (lys276del) increased MAST1 binding to microtubules compared to controls. Mutant mice heterozygous for a Mast1 leu278del allele showed a thicker corpus callosum compared to wildtype, and an overall reduction in cortical volume and thickness and decreased cerebellar volume and number of granule and Purkinje cells due to increased apoptosis compared to controls.

1 Emirati patient with ID, microcephaly, and dysmorphic features, with missense variant in MAST1.
Sources: Literature
Mendeliome v0.287 MACROD2 Zornitza Stark gene: MACROD2 was added
gene: MACROD2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: MACROD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MACROD2 were set to 31055587
Phenotypes for gene: MACROD2 were set to intellectual disability; dysmorphic features; microcephaly
Review for gene: MACROD2 was set to RED
Added comment: 1 family with a few affected with microcephaly, ID, dysmorphic features, and polydactyly. Deletion of chromosome 20p12.1 involving the MACROD2 gene was found in several members of the family. qRT-PCR showed higher levels of a MACROD2 mRNA isoform in the individuals carrying the deletion.
Sources: Literature
Mendeliome v0.285 LSS Zornitza Stark gene: LSS was added
gene: LSS was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: LSS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSS were set to 30723320
Phenotypes for gene: LSS were set to Cataract 44, OMIM #616509; Hypotrichosis 14, OMIM #618275; Intellectual disability
Review for gene: LSS was set to GREEN
Added comment: Expanded the phenotypic spectrum of LSS to a recessive neuroectodermal syndrome formerly named alopecia with mental retardation (APMR) syndrome. Ten APMR individuals from 6 unrelated families with biallelic variants in LSS. Quantification of cholesterol and its precursors did not reveal noticeable imbalance.
Sources: Literature
Mendeliome v0.283 LMAN2L Zornitza Stark Gene: lman2l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.283 LMAN2L Zornitza Stark Classified gene: LMAN2L as Amber List (moderate evidence)
Mendeliome v0.283 LMAN2L Zornitza Stark Gene: lman2l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.282 LMAN2L Zornitza Stark gene: LMAN2L was added
gene: LMAN2L was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: LMAN2L was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: LMAN2L were set to 31020005; 26566883
Phenotypes for gene: LMAN2L were set to Mental retardation, autosomal recessive, 52; OMIM #616887
Review for gene: LMAN2L was set to AMBER
Added comment: 1 consanguineous family with 7 individuals with ID and epilepsy, with homozygous LMAN2L missense mutation. Segregated with disease in family, and unaffected family members were heterozygous variant carriers. No functional studies.

1 non-consanguineous family with 4 affected with heterozygous frameshift LMAN2L mutation. Segregates in family. Mutation eliminates LMAN2L's endoplasmic reticulum retention signal and mislocalizes the protein from that compartment to the plasma membrane.
Sources: Literature
Mendeliome v0.272 FRY Zornitza Stark Gene: fry has been classified as Amber List (Moderate Evidence).
Mendeliome v0.272 FRY Zornitza Stark Classified gene: FRY as Amber List (moderate evidence)
Mendeliome v0.272 FRY Zornitza Stark Gene: fry has been classified as Amber List (Moderate Evidence).
Mendeliome v0.271 FRY Zornitza Stark gene: FRY was added
gene: FRY was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: FRY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRY were set to 31487712; 27457812; 21937992
Phenotypes for gene: FRY were set to Intellectual disability
Review for gene: FRY was set to AMBER
Added comment: 1 patient with ID/DD and a novel homozygous deletion involving FRY gene identified by genomic SNP microarray. No functional evidence.

2 consanguineous families with 6 affected individuals with ID, and homozygous mutations of FRY. No functional evidence.
Sources: Literature
Mendeliome v0.266 EEF1D Zornitza Stark Gene: eef1d has been classified as Amber List (Moderate Evidence).
Mendeliome v0.266 EEF1D Zornitza Stark Classified gene: EEF1D as Amber List (moderate evidence)
Mendeliome v0.266 EEF1D Zornitza Stark Gene: eef1d has been classified as Amber List (Moderate Evidence).
Mendeliome v0.265 EEF1D Zornitza Stark gene: EEF1D was added
gene: EEF1D was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: EEF1D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEF1D were set to 30787422; 28097321
Phenotypes for gene: EEF1D were set to Intellectual disability
Review for gene: EEF1D was set to AMBER
Added comment: Two unrelated families reported; one as part of a very large cohort of consanguineous families reporting multiple new candidate genes. No functional data.
Sources: Literature
Mendeliome v0.246 RNF113A Zornitza Stark Gene: rnf113a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.243 RNF113A Zornitza Stark Classified gene: RNF113A as Amber List (moderate evidence)
Mendeliome v0.243 RNF113A Zornitza Stark Gene: rnf113a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.242 RNF113A Zornitza Stark reviewed gene: RNF113A: Rating: AMBER; Mode of pathogenicity: None; Publications: 25612912, 31793730; Phenotypes: Trichothiodystrophy 5, nonphotosensitive, OMIM #300953; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.240 SEMA5A Zornitza Stark Gene: sema5a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.240 SEMA5A Zornitza Stark Classified gene: SEMA5A as Amber List (moderate evidence)
Mendeliome v0.240 SEMA5A Zornitza Stark Gene: sema5a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.239 SEMA5A Zornitza Stark gene: SEMA5A was added
gene: SEMA5A was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: SEMA5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEMA5A were set to 26395558
Phenotypes for gene: SEMA5A were set to Intellectual disability; autism
Review for gene: SEMA5A was set to AMBER
Added comment: 1 patient with de novo translocation t(5;22)(p15.3;q11.21) and ASD and ID. At the translocation breakpoint on chromosome 5, they observed a 861-kb deletion encompassing the end of the SEMA5A gene. No functional studies.

2 patients with ASD and predicted deleterious heterozygous variants (maternally inherited). No functional studies
Sources: Literature
Mendeliome v0.220 ACTL6B Zornitza Stark gene: ACTL6B was added
gene: ACTL6B was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: ACTL6B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACTL6B were set to 31134736; 31031012; 30656450; 30237576
Phenotypes for gene: ACTL6B were set to Epileptic encephalopathy, early infantile, 76, MIM# 618468; Intellectual developmental disorder with severe speech and ambulation defects, MIM# 618470
Review for gene: ACTL6B was set to GREEN
Added comment: Over 10 unrelated individuals reported in the literature.
Sources: Literature
Mendeliome v0.219 SELENOI Zornitza Stark Gene: selenoi has been classified as Amber List (Moderate Evidence).
Mendeliome v0.217 SELENOI Zornitza Stark Classified gene: SELENOI as Amber List (moderate evidence)
Mendeliome v0.217 SELENOI Zornitza Stark Gene: selenoi has been classified as Amber List (Moderate Evidence).
Mendeliome v0.216 SELENOI Zornitza Stark reviewed gene: SELENOI: Rating: AMBER; Mode of pathogenicity: None; Publications: 28052917; Phenotypes: developmental delay, spasticity, periventricular white mater abnormalities, peripheral neuropathy, seizures, bifid uvula in some affected individuals, microcephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.214 PHC1 Zornitza Stark Gene: phc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.211 PHC1 Zornitza Stark Classified gene: PHC1 as Amber List (moderate evidence)
Mendeliome v0.211 PHC1 Zornitza Stark Gene: phc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.210 PHC1 Zornitza Stark reviewed gene: PHC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23418308; Phenotypes: Microcephaly 11, primary, autosomal recessive, MIM#615414; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.193 NECAP1 Zornitza Stark Gene: necap1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.190 NECAP1 Zornitza Stark Classified gene: NECAP1 as Amber List (moderate evidence)
Mendeliome v0.190 NECAP1 Zornitza Stark Gene: necap1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.186 NDUFB9 Zornitza Stark Gene: ndufb9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.183 NDUFB9 Zornitza Stark Classified gene: NDUFB9 as Amber List (moderate evidence)
Mendeliome v0.183 NDUFB9 Zornitza Stark Gene: ndufb9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.182 NDUFB9 Zornitza Stark reviewed gene: NDUFB9: Rating: AMBER; Mode of pathogenicity: None; Publications: 22200994; Phenotypes: Mitochondrial complex I deficiency, nuclear type 24, MIM#618245; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.182 MRPS16 Zornitza Stark Gene: mrps16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.182 MRPS16 Zornitza Stark Gene: mrps16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.182 MRPS16 Zornitza Stark Phenotypes for gene: MRPS16 were changed from to Combined oxidative phosphorylation deficiency 2; OMIM #610498
Mendeliome v0.179 MRPS16 Zornitza Stark Classified gene: MRPS16 as Amber List (moderate evidence)
Mendeliome v0.179 MRPS16 Zornitza Stark Gene: mrps16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.177 MRPL3 Zornitza Stark Gene: mrpl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.177 MRPL3 Zornitza Stark Phenotypes for gene: MRPL3 were changed from to Combined oxidative phosphorylation deficiency 9; OMIM #614582
Mendeliome v0.174 MRPL3 Zornitza Stark Classified gene: MRPL3 as Amber List (moderate evidence)
Mendeliome v0.174 MRPL3 Zornitza Stark Gene: mrpl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.170 CDK16 Zornitza Stark Gene: cdk16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.170 CDK16 Zornitza Stark Classified gene: CDK16 as Amber List (moderate evidence)
Mendeliome v0.170 CDK16 Zornitza Stark Gene: cdk16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.169 CDK16 Zornitza Stark gene: CDK16 was added
gene: CDK16 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: CDK16 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CDK16 were set to 25644381
Phenotypes for gene: CDK16 were set to Intellectual disability
Review for gene: CDK16 was set to AMBER
Added comment: Single family described in this manuscript describing multiple candidate genes for XLID.
Sources: Expert list
Mendeliome v0.146 CFAP57 Sebastian Lunke Classified gene: CFAP57 as Amber List (moderate evidence)
Mendeliome v0.146 CFAP57 Sebastian Lunke Gene: cfap57 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.145 CFAP57 Sebastian Lunke reviewed gene: CFAP57: Rating: AMBER; Mode of pathogenicity: None; Publications: bioRxiv 773028, doi: https://doi.org/10.1101/773028; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.145 EXOSC2 Zornitza Stark Gene: exosc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.142 EXOSC2 Zornitza Stark Classified gene: EXOSC2 as Amber List (moderate evidence)
Mendeliome v0.142 EXOSC2 Zornitza Stark Gene: exosc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.109 COX14 Zornitza Stark Gene: cox14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.106 COX14 Zornitza Stark Classified gene: COX14 as Amber List (moderate evidence)
Mendeliome v0.106 COX14 Zornitza Stark Gene: cox14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.102 CEP63 Zornitza Stark Gene: cep63 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.99 CEP63 Zornitza Stark Classified gene: CEP63 as Amber List (moderate evidence)
Mendeliome v0.99 CEP63 Zornitza Stark Gene: cep63 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.97 CDK6 Zornitza Stark Gene: cdk6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.94 CDK6 Zornitza Stark Classified gene: CDK6 as Amber List (moderate evidence)
Mendeliome v0.94 CDK6 Zornitza Stark Gene: cdk6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.92 CD96 Zornitza Stark Gene: cd96 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.89 CD96 Zornitza Stark Classified gene: CD96 as Amber List (moderate evidence)
Mendeliome v0.89 CD96 Zornitza Stark Gene: cd96 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.79 CCDC78 Zornitza Stark Gene: ccdc78 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.76 CCDC78 Zornitza Stark Classified gene: CCDC78 as Amber List (moderate evidence)
Mendeliome v0.76 CCDC78 Zornitza Stark Gene: ccdc78 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.64 BBIP1 Zornitza Stark Gene: bbip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.64 BBIP1 Zornitza Stark Classified gene: BBIP1 as Amber List (moderate evidence)
Mendeliome v0.64 BBIP1 Zornitza Stark Gene: bbip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.53 TTI1 Sebastian Lunke Gene: tti1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.53 TTI1 Sebastian Lunke Classified gene: TTI1 as Amber List (moderate evidence)
Mendeliome v0.53 TTI1 Sebastian Lunke Gene: tti1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.30 HCN2 Zornitza Stark Gene: hcn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.30 HCN2 Zornitza Stark Classified gene: HCN2 as Amber List (moderate evidence)
Mendeliome v0.30 HCN2 Zornitza Stark Gene: hcn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.24 MASTL Zornitza Stark Gene: mastl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.24 MASTL Zornitza Stark Classified gene: MASTL as Amber List (moderate evidence)
Mendeliome v0.24 MASTL Zornitza Stark Gene: mastl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.22 PCLO Zornitza Stark Gene: pclo has been classified as Amber List (Moderate Evidence).
Mendeliome v0.22 PCLO Zornitza Stark Classified gene: PCLO as Amber List (moderate evidence)
Mendeliome v0.22 PCLO Zornitza Stark Gene: pclo has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11 PNPLA4 Zornitza Stark Classified gene: PNPLA4 as Amber List (moderate evidence)
Mendeliome v0.11 PNPLA4 Zornitza Stark Gene: pnpla4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6 ASTN2 Zornitza Stark Gene: astn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6 ASTN2 Zornitza Stark Classified gene: ASTN2 as Amber List (moderate evidence)
Mendeliome v0.6 ASTN2 Zornitza Stark Gene: astn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5 ASTN2 Zornitza Stark Classified gene: ASTN2 as Amber List (moderate evidence)
Mendeliome v0.5 ASTN2 Zornitza Stark Gene: astn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4 ASTN2 Zornitza Stark reviewed gene: ASTN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 28940097; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.0 STAMBP Zornitza Stark gene: STAMBP was added
gene: STAMBP was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: STAMBP was set to Unknown
Mendeliome v0.0 PSMB9 Zornitza Stark gene: PSMB9 was added
gene: PSMB9 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PSMB9 was set to Unknown
Mendeliome v0.0 PSMB8 Zornitza Stark gene: PSMB8 was added
gene: PSMB8 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PSMB8 was set to Unknown
Mendeliome v0.0 PSMB4 Zornitza Stark gene: PSMB4 was added
gene: PSMB4 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PSMB4 was set to Unknown
Mendeliome v0.0 MSMB Zornitza Stark gene: MSMB was added
gene: MSMB was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MSMB was set to Unknown
Mendeliome v0.0 MBTPS2 Zornitza Stark gene: MBTPS2 was added
gene: MBTPS2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MBTPS2 was set to Unknown
Mendeliome v0.0 MBOAT7 Zornitza Stark gene: MBOAT7 was added
gene: MBOAT7 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MBOAT7 was set to Unknown
Mendeliome v0.0 MBNL1 Zornitza Stark gene: MBNL1 was added
gene: MBNL1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MBNL1 was set to Unknown
Mendeliome v0.0 MBL2 Zornitza Stark gene: MBL2 was added
gene: MBL2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MBL2 was set to Unknown
Mendeliome v0.0 MBD5 Zornitza Stark gene: MBD5 was added
gene: MBD5 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MBD5 was set to Unknown
Mendeliome v0.0 LMBRD1 Zornitza Stark gene: LMBRD1 was added
gene: LMBRD1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LMBRD1 was set to Unknown
Mendeliome v0.0 LMBR1 Zornitza Stark gene: LMBR1 was added
gene: LMBR1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LMBR1 was set to Unknown
Mendeliome v0.0 LAMB3 Zornitza Stark gene: LAMB3 was added
gene: LAMB3 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LAMB3 was set to Unknown
Mendeliome v0.0 LAMB2 Zornitza Stark gene: LAMB2 was added
gene: LAMB2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LAMB2 was set to Unknown
Mendeliome v0.0 LAMB1 Zornitza Stark gene: LAMB1 was added
gene: LAMB1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LAMB1 was set to Unknown
Mendeliome v0.0 KCNMB1 Zornitza Stark gene: KCNMB1 was added
gene: KCNMB1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: KCNMB1 was set to Unknown
Mendeliome v0.0 IGHMBP2 Zornitza Stark gene: IGHMBP2 was added
gene: IGHMBP2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: IGHMBP2 was set to Unknown
Mendeliome v0.0 HMBS Zornitza Stark gene: HMBS was added
gene: HMBS was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: HMBS was set to Unknown
Mendeliome v0.0 GPNMB Zornitza Stark gene: GPNMB was added
gene: GPNMB was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GPNMB was set to Unknown
Mendeliome v0.0 AMBN Zornitza Stark gene: AMBN was added
gene: AMBN was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: AMBN was set to Unknown