ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.8993C>G (p.Ser2998Cys)

gnomAD frequency: 0.00001  dbSNP: rs559922535
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000152588 SCV000201858 likely benign not specified 2013-11-06 criteria provided, single submitter clinical testing Ser2998Cys in Exon 45 of USH2A: This variant is not expected to have clinical si gnificance because the serine (Ser) residue at position 2998 is poorly conserved across species, with hedgehog, wallaby, and opossum having a cysteine (Cys) at this position. In addition, computational analyses (SIFT, PolyPhen2, and AlignGV GD) suggest that the variant may not impact the protein.
Counsyl RCV000671038 SCV000795977 uncertain significance Usher syndrome type 2A; Retinitis pigmentosa 39 2017-11-26 criteria provided, single submitter clinical testing
Invitae RCV001307268 SCV001496673 uncertain significance not provided 2022-09-07 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2998 of the USH2A protein (p.Ser2998Cys). This variant is present in population databases (rs559922535, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 166466). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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