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| Mendeliome v1.1660 | TRPV5 |
Sangavi Sivagnanasundram changed review comment from: Not a well-established gene-disease association. Has only been reported in one consanguineous family. PMID: 38528055 3 individuals from the same family affected with hypercalciuria. Biallelic Met598Val variant was identified in the proband and his two affect sibs Functional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used. Sources: Other; to: Not a well-established gene-disease association. Has only been reported in one consanguineous family. PMID: 38528055 3 individuals from the same family affected with hypercalciuria. Biallelic Met598Val variant was identified in the proband and his two affect sibs Functional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used. PMID: 14679186 TRPV5 knockout mice model was used to assess whether the abolishment of TRPV5 led to a disruption in Ca2+ handling. The effects of the disruption in Ca2+ handling resulted in bone abnormalities in the mice and is likely the cause of idiopathic hypercalciuria. Sources: Other |
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| Mendeliome v1.992 | ANO1 | Zornitza Stark edited their review of gene: ANO1: Added comment: PMID 37253099: screening analysis of Moyamoya disease (MMD) cohort revealed 8 individuals with variants in the ANO1 gene. Two families had the same rare variant p.Met658Val. The ANO1 rare variants were assessed using patch-clamp recordings, and the majority of variants, including ANO1 p.Met658Val, displayed increased sensitivity to intracellular Ca2+. Patients harboring these gain-of-function ANO1 variants had classic features of MMD, but also had aneurysm, stenosis, and/or occlusion in the posterior circulation. Amber rating due to somewhat conflicting segregation and functional data presented.; Changed publications: 37253099; Changed phenotypes: Intestinal dysmotility syndrome, MIM# 620045, Moyamoya disease, MONDO:0016820, ANO1 related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.956 | MIR204 |
Chern Lim gene: MIR204 was added gene: MIR204 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MIR204 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MIR204 were set to 26056285; 37321975 Phenotypes for gene: MIR204 were set to Retinal dystrophy and iris coloboma with or without cataract (MIM#616722) Mode of pathogenicity for gene: MIR204 was set to Other Review for gene: MIR204 was set to GREEN gene: MIR204 was marked as current diagnostic Added comment: PMID: 26056285 - Bilateral coloboma and rod-cone dystrophy with or without cataract in nine individuals of a five-generation family. - Heterozygous n.37C>T segregates with the disease in all affected individuals. - Functional analysis including transcriptome analysis showed this variant resulted in significant alterations of miR-204 targeting capabilities. In vivo injection, in medaka fish (Oryzias latipes), of the mutated miR-204 caused a phenotype consistent with that observed in the family. - Authors suggested gain of function is the likely disease mechanism. PMID: 37321975 - Four members of a three-generation family with early-onset chorioretinal dystrophy, heterozygous for n.37C>T. - Additionally, four family members were shown to be affected by albinism resulting from biallelic pathogenic OCA2 variants. - Haplotype analysis excluded relatedness with the family reported in PMID: 26056285. - In silico analysis of the MIR204 n.37C>T variant reveals profound changes to its target mRNAs and suggests a gain-of-function mechanism of miR 204 variant. Sources: Literature |
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| Mendeliome v1.541 | TNNC2 |
Zornitza Stark gene: TNNC2 was added gene: TNNC2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TNNC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TNNC2 were set to 33755597 Phenotypes for gene: TNNC2 were set to Congenital myopathy, MONDO:0019952, TNNC2-related Review for gene: TNNC2 was set to GREEN Added comment: Two families reported: Family 1: 4 individuals, three generations; missense variant p.(Asp34Tyr) Family 2: de novo variant, missense p.(Met79Ile) Physiological studies in myofibers isolated from patients’ biopsies revealed a markedly reduced force response of the sarcomeres to [Ca2+]. This pathomechanism was further confirmed in experiments in which contractile dysfunction was evoked by replacing TnC in myofibers from healthy control subjects with recombinant, mutant TnC. Conversely, the contractile dysfunction of myofibers from patients was repaired by replacing endogenous, mutant TnC with recombinant, wild-type TnC. Borderline Green: sufficient segregation in Fam 1 plus de novo status in Fam 2, plus functional data. Sources: Literature |
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| Mendeliome v1.410 | CA2 | Zornitza Stark Tag treatable tag was added to gene: CA2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.114 | PNPT1 | Zornitza Stark edited their review of gene: PNPT1: Added comment: Three families reported with heterozygous variants and SCA25. Incomplete penetrance in one of the families. In the third family, the variant was inherited from an asymptomatic 80+ year old. Note bi-allelic variants in this gene cause a mitochondrial disorder. Exact mechanism through which mono-allelic variants cause SCA25 not elucidated: authors speculate abnormal accumulation of mitochondrial RNA with subsequent leakage into the cytosol that may trigger a type 1 interferon response leading to neuroinflammation with neuronal dysfunction or neuronal loss.; Changed rating: AMBER; Changed publications: 35411967; Changed phenotypes: Spinocerebellar ataxia 25, MIM# 608703; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12154 | CA2 | Zornitza Stark Phenotypes for gene: CA2 were changed from to Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM#259730 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12153 | CA2 | Zornitza Stark Mode of inheritance for gene: CA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12152 | CA2 | Zornitza Stark Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12088 | CA2 | Ain Roesley Publications for gene: CA2 were set to 34624559; 33555497; 12566520; 7627193 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12084 | CA2 | Ain Roesley Publications for gene: CA2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12083 | CA2 | Ain Roesley Marked gene: CA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12083 | CA2 | Ain Roesley Gene: ca2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12083 | CA2 | Ain Roesley reviewed gene: CA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34624559, 33555497, 12566520, 7627193; Phenotypes: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM#259730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9542 | Zornitza Stark removed gene:BRCA2 from the panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9537 | BRCA2 |
Krithika Murali gene: BRCA2 was added gene: BRCA2 was added to Mendeliome. Sources: Expert list,Literature Mode of inheritance for gene: BRCA2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: BRCA2 were set to Fanconi anemia, complementation group D1 - MIM# 605724 Review for gene: BRCA2 was set to GREEN Added comment: Well-established gene disease association Sources: Expert list, Literature |
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| Mendeliome v0.7459 | SMARCA2 | Zornitza Stark Phenotypes for gene: SMARCA2 were changed from Nicolaides-Baraitser syndrome, MIM #601358; Blepharophimosis-intellectual disability syndrome to Nicolaides-Baraitser syndrome, MIM #601358; Blepharophimosis-intellectual disability syndrome, MIM#619293 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6817 | SCA2 | Bryony Thompson Marked STR: SCA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6817 | SCA2 | Bryony Thompson Str: sca2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6817 | SCA2 | Bryony Thompson Classified STR: SCA2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6817 | SCA2 | Bryony Thompson Str: sca2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6816 | SCA2 |
Bryony Thompson STR: SCA2 was added STR: SCA2 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: SCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA2 were set to 29325606; 20301452 Phenotypes for STR: SCA2 were set to Spinocerebellar ataxia 2 MIM#183090 Review for STR: SCA2 was set to GREEN STR: SCA2 was marked as clinically relevant Added comment: NM_002973.3:c.496_498CAG[X] Toxic protein aggregation is mechanism of disease Benign: ≤31 repeats (homozygous 31/31 repeats reported for recessive SCA2) Uncertain: 32 repeats ALS risk allele: 30-32 repeats Reduced penetrance: 33-34 repeats, may not develop symptoms or only very late in life Full penetrance: ≥35 repeats Interruption of a CAG expanded allele by a CAA repeat does not mitigate the pathogenicity of the repeat size, but may enhance the meiotic stability of the repeat Sources: Expert list |
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| Mendeliome v0.4460 | ISCA2 | Zornitza Stark Marked gene: ISCA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4460 | ISCA2 | Zornitza Stark Gene: isca2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4460 | ISCA2 | Zornitza Stark Phenotypes for gene: ISCA2 were changed from to Multiple mitochondrial dysfunctions syndrome 4, MIM# 616370 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4459 | ISCA2 | Zornitza Stark Publications for gene: ISCA2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4458 | ISCA2 | Zornitza Stark Mode of inheritance for gene: ISCA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4457 | ISCA2 | Zornitza Stark reviewed gene: ISCA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25539947, 29297947, 29122497, 29359243; Phenotypes: Multiple mitochondrial dysfunctions syndrome 4, MIM# 616370; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4314 | OCA2 | Zornitza Stark Phenotypes for gene: OCA2 were changed from [Skin/hair/eye pigmentation 1, blond/brown hair] 227220; [Skin/hair/eye pigmentation 1, blue/nonblue eyes] 227220; Albinism, brown oculocutaneous 203200; Albinism, oculocutaneous, type II 203200; autosomal dominant Albinism, oculocutaneous to Albinism, brown oculocutaneous 203200; Albinism, oculocutaneous, type II 203200; autosomal dominant Albinism, oculocutaneous | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4313 | OCA2 | Zornitza Stark Publications for gene: OCA2 were set to 32741191; 24518832 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4312 | OCA2 | Zornitza Stark Tag SV/CNV tag was added to gene: OCA2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4312 | OCA2 | Zornitza Stark Marked gene: OCA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4312 | OCA2 | Zornitza Stark Gene: oca2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4312 | OCA2 | Zornitza Stark Phenotypes for gene: OCA2 were changed from to [Skin/hair/eye pigmentation 1, blond/brown hair] 227220; [Skin/hair/eye pigmentation 1, blue/nonblue eyes] 227220; Albinism, brown oculocutaneous 203200; Albinism, oculocutaneous, type II 203200; autosomal dominant Albinism, oculocutaneous | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4311 | OCA2 | Zornitza Stark Publications for gene: OCA2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4310 | OCA2 | Zornitza Stark Mode of inheritance for gene: OCA2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4309 | OCA2 | Elena Savva reviewed gene: OCA2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32741191, 24518832; Phenotypes: [Skin/hair/eye pigmentation 1, blond/brown hair] 227220, [Skin/hair/eye pigmentation 1, blue/nonblue eyes] 227220, Albinism, brown oculocutaneous 203200, Albinism, oculocutaneous, type II 203200, autosomal dominant Albinism, oculocutaneous; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3517 | SMARCA2 | Zornitza Stark Marked gene: SMARCA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3517 | SMARCA2 | Zornitza Stark Gene: smarca2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3517 | SMARCA2 | Zornitza Stark Phenotypes for gene: SMARCA2 were changed from to Nicolaides-Baraitser syndrome, MIM #601358; Blepharophimosis-intellectual disability syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3516 | SMARCA2 | Zornitza Stark Publications for gene: SMARCA2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3515 | SMARCA2 | Zornitza Stark Mode of pathogenicity for gene: SMARCA2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3514 | SMARCA2 | Zornitza Stark Mode of inheritance for gene: SMARCA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3513 | SMARCA2 | Zornitza Stark reviewed gene: SMARCA2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 26468571, 32694869; Phenotypes: Nicolaides-Baraitser syndrome, MIM #601358, Blepharophimosis-intellectual disability syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3319 | ABCA2 | Zornitza Stark Marked gene: ABCA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3319 | ABCA2 | Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3319 | ABCA2 | Zornitza Stark Classified gene: ABCA2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3319 | ABCA2 | Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3318 | ABCA2 |
Zornitza Stark gene: ABCA2 was added gene: ABCA2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ABCA2 were set to 30237576; 29302074; 31047799 Phenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808 Review for gene: ABCA2 was set to GREEN Added comment: Biallelic pathogenic ABCA2 variants cause Intellectual developmental disorder with poor growth and with or without seizures or ataxia (MIM 618808). There are 3 relevant publications (01-07-2020) : - Maddirevula et al [2019 - PMID: 30237576] described briefly 2 unrelated subjects (16-2987, 16DG0071) both DD and seizures among other manifestations. - Hu et al [2019 - PMID: 29302074] reported 3 sibs (M8600615 - III:1-3) born to consanguineous parents (M8600615 - III:1-3) with DD/ID (formal confirmation of moderate ID, in those (2) evaluated). One also presented with seizures. - Aslam and Naz [2019 - PMID: 31047799] provided clinical details on 2 siblings born to consanguineous parents. ID was reported for the older sib but was absent in the younger one. Seizures were not part of the phenotype. All subjects harbored biallelic pLoF variants. N.B. : Steinberg et al [2015 - PMID: 25773295], within a cohort of patients with ALS, identified one with biallelic ABCA2 variants. As however Aslam and Naz comment, this person harbored a single pathogenic variant, with a second one rather unlikely to be pathogenic due to high allele frequency. Overall this gene can be considered for inclusion with green rating in both ID and epilepsy panels (each in >=3 unrelated individuals). Sources: Expert Review |
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| Mendeliome v0.0 | SMARCA2 |
Zornitza Stark gene: SMARCA2 was added gene: SMARCA2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: SMARCA2 was set to Unknown |
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| Mendeliome v0.0 | OCA2 |
Zornitza Stark gene: OCA2 was added gene: OCA2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: OCA2 was set to Unknown |
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| Mendeliome v0.0 | ISCA2 |
Zornitza Stark gene: ISCA2 was added gene: ISCA2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: ISCA2 was set to Unknown |
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| Mendeliome v0.0 | CA2 |
Zornitza Stark gene: CA2 was added gene: CA2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: CA2 was set to Unknown |
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