ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.8232G>C (p.Trp2744Cys)

gnomAD frequency: 0.00001  dbSNP: rs1424639717
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001052468 SCV001216680 pathogenic not provided 2023-12-19 criteria provided, single submitter clinical testing This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 2744 of the USH2A protein (p.Trp2744Cys). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with Usher syndrome (PMID: 21686329, 26338283, 29625443, 29641573). 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: 848662). 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 RCV001075376 SCV001240997 pathogenic Retinal dystrophy 2018-06-12 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001052468 SCV002021609 likely pathogenic not provided 2020-11-03 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003396674 SCV004103001 pathogenic USH2A-related condition 2024-01-02 criteria provided, single submitter clinical testing The USH2A c.8232G>C variant is predicted to result in the amino acid substitution p.Trp2744Cys. This variant was reported in the compound heterozygous and homozygous states in multiple individuals with retinitis pigmentosa or Usher syndrome (Xu. 2011. PubMed ID: 21686329; Gao. 2021. PubMed ID: 32188678; Table S5, Huang. 2018. PubMed ID: 29641573; Sun. 2020. PubMed ID: 32100970). This variant is reported in 0.0055% of alleles in individuals of East Asian descent in gnomAD. This variant is interpreted as pathogenic.
Genome-Nilou Lab RCV003455229 SCV004182829 likely pathogenic Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003455228 SCV004182831 likely pathogenic Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing

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