ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.9882C>G (p.Cys3294Trp)

gnomAD frequency: 0.00003  dbSNP: rs749228276
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000593818 SCV000704988 uncertain significance not provided 2017-02-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000593818 SCV001206278 pathogenic not provided 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 3294 of the USH2A protein (p.Cys3294Trp). This variant is present in population databases (rs749228276, gnomAD 0.008%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 24043777, 28041643, 28130426). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 438036). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt USH2A protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001075611 SCV001241238 pathogenic Retinal dystrophy 2019-01-31 criteria provided, single submitter clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear RCV001376250 SCV001573327 uncertain significance Retinitis pigmentosa 39 2021-04-08 criteria provided, single submitter research The USH2A c.9882C>G variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2, PP1. Based on this evidence we have classified this variant as Variant of Uncertain Significance.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV000504661 SCV001950425 uncertain significance Retinitis pigmentosa 2021-04-01 criteria provided, single submitter curation The p.Cys3294Trp variant in USH2A was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PM2, PP1. Based on this evidence we have classified this variant as a Variant of Uncertain Significance. If you have any questions about the classification please reach out to the Pierce Lab.
Myriad Genetics, Inc. RCV001810454 SCV002060011 likely pathogenic Usher syndrome type 2A 2021-11-16 criteria provided, single submitter clinical testing NM_206933.2(USH2A):c.9882C>G(C3294W) is a missense variant classified as likely pathogenic in the context of USH2A-related disorders. Please note that C3294W is associated with retinitis pigmentosa. C3294W has been observed in cases with relevant disease (PMID: 24043777, 28041643, 25412400, 28130426, 32646269, 34031601). Functional assessments of this variant are not available in the literature. C3294W has been observed in population frequency databases (gnomAD: NFE 0.009%). In summary, NM_206933.2(USH2A):c.9882C>G(C3294W) is a missense variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Baylor Genetics RCV001376250 SCV005055711 pathogenic Retinitis pigmentosa 39 2024-03-04 criteria provided, single submitter clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504661 SCV000598846 likely pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research

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