ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.6163G>A (p.Ala2055Thr)

dbSNP: rs768233523
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001208722 SCV001380127 uncertain significance not provided 2022-06-05 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2055 of the USH2A protein (p.Ala2055Thr). This variant also falls at the last nucleotide of exon 31, which is part of the consensus splice site for this exon. This variant is present in population databases (rs768233523, gnomAD 0.002%). 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: 939338). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001724266 SCV001950429 uncertain significance Retinitis pigmentosa 2021-04-01 criteria provided, single submitter curation The p.Ala2055Thr 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, PP3, PM3-P. 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001208722 SCV004025976 uncertain significance not provided 2022-02-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003449654 SCV004181699 uncertain significance Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001828672 SCV004181700 uncertain significance Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Natera, Inc. RCV001828672 SCV002090897 uncertain significance Usher syndrome type 2A 2020-07-28 no assertion criteria provided clinical testing

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