ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.14285A>G (p.Asn4762Ser)

gnomAD frequency: 0.00001  dbSNP: rs1254637647
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ocular Genomics Institute, Massachusetts Eye and Ear RCV001376408 SCV001573534 likely pathogenic Retinitis pigmentosa 39 2021-04-08 criteria provided, single submitter research The USH2A c.14285A>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, PM3, PM1. Based on this evidence we have classified this variant as Likely Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001871988 SCV002244262 pathogenic not provided 2023-07-16 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 4762 of the USH2A protein (p.Asn4762Ser). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with retinitis pigmentosa and/or Usher syndrome (PMID: 22135276, 24938718, 29641573, 32100970). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1065734). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on USH2A protein function. This variant disrupts the p.Asn4762 amino acid residue in USH2A. Other variant(s) that disrupt this residue have been observed in individuals with USH2A-related conditions (PMID: 30073356; Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV001376408 SCV004183086 likely pathogenic Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV001376408 SCV004208355 pathogenic Retinitis pigmentosa 39 2023-08-03 criteria provided, single submitter clinical testing

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