ClinVar Miner

Submissions for variant NM_021954.4(GJA3):c.184G>A (p.Glu62Lys)

dbSNP: rs2141138365
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001797193 SCV002038860 likely pathogenic not provided 2022-08-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25148791, 35008666, 32143568)
Labcorp Genetics (formerly Invitae), Labcorp RCV001542775 SCV003442017 pathogenic Cataract 14 multiple types 2024-09-06 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 62 of the GJA3 protein (p.Glu62Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant congenital cataracts (PMID: 25148791; internal data). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1184602). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt GJA3 protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Dept. Genetics and Cancer, Menzies Institute for Medical Research, University of Tasmania RCV001542775 SCV005081792 likely pathogenic Cataract 14 multiple types 2023-01-21 criteria provided, single submitter curation Variant identified and curated during a GJA3 specific review of the literature in relation to pediatric or congenital cataract. ACMG-AMP criteria applied: PM1, PM5, PM2(Supporting), PP3. Original variant report: PMID:25148791. Gene review and curation guidelines are outlined in: https://doi.org/10.1080/17469899.2023.2160320
Genomics England Pilot Project, Genomics England RCV001542775 SCV001760314 likely pathogenic Cataract 14 multiple types no assertion criteria provided clinical testing

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