ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.949C>A (p.Arg317=)

gnomAD frequency: 0.00003  dbSNP: rs111033272
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Total submissions: 20
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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 RCV000824799 SCV000065652 pathogenic Rare genetic deafness 2012-11-19 criteria provided, single submitter clinical testing The p.Arg317Arg (NM_206933.2 c.949C>A) variant in USH2A has been reported in 9 i ndividuals with Usher syndrome (Pennings 2004, Seyedahmadi 2004, Cremers 2007, D reyer 2008, Vache 2010, Bonnet 2011). A second variant in USH2A was found in tr ans in at least 3 of these individuals (Pennings 2004, Vache 2010, Bonnet 2011). This variant has also been reported in ClinVar (Variation ID#2358) as pathogeni c. mRNA studies show that this variant leads to abnormal splicing and a frameshi ft (Vache 2010). This variant has been identified in (8/126206) of European chro mosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute .org; dbSNP rs111033272). Although this variant has been seen in the general pop ulation, its frequency is low enough to be consistent with a recessive carrier f requency. In summary, this variant meets criteria to be classified as pathogenic for Usher syndrome in an autosomal recessive manner based upon functional evide nce and its occurrence in individuals with this disease. ACMG/AMP Criteria appli ed: PVS1, PM2, PM3, PP5.
Eurofins Ntd Llc (ga) RCV000412796 SCV000339779 pathogenic not provided 2016-04-01 criteria provided, single submitter clinical testing
GeneDx RCV000412796 SCV000490867 pathogenic not provided 2020-02-05 criteria provided, single submitter clinical testing Non-canonical splice site variant demonstrated to result in loss-of-function (Vache et al., 2010); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 27957503, 15043528, 15015129, 30904819, 20513143, 26927203, 24944099, 23891399, 28944237, 15241801, 15325563, 21569298, 18273898, 16963483, 25575603, 30609409)
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000627017 SCV000747720 pathogenic Blindness; Rod-cone dystrophy; Pigmentary retinopathy; Abnormal macular morphology; Retinal pigment epithelial atrophy 2017-01-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000763297 SCV000893962 pathogenic Usher syndrome type 2A; Retinitis pigmentosa 39 2018-10-31 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory, Institute for Ophthalmic Research RCV001199595 SCV001162766 pathogenic Usher syndrome type 2 2020-01-09 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV000412796 SCV001219336 pathogenic not provided 2024-01-08 criteria provided, single submitter clinical testing This sequence change affects codon 317 of the USH2A mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the USH2A protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs111033272, gnomAD 0.006%). This variant has been observed in individual(s) with Usher syndrome type IIa or nonsydromic retinitis pigmentosa (PMID: 15241801, 20513143, 21569298, 26927203). 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: 2358). Studies have shown that this variant results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 20513143). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001075725 SCV001241353 pathogenic Retinal dystrophy 2019-05-09 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000412796 SCV001248865 pathogenic not provided 2019-08-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000002452 SCV001369018 pathogenic Usher syndrome type 2A 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic.
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV000412796 SCV001448877 pathogenic not provided 2017-09-26 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000984234 SCV004182925 pathogenic Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000002452 SCV004182926 pathogenic Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV000984234 SCV004208204 pathogenic Retinitis pigmentosa 39 2024-03-08 criteria provided, single submitter clinical testing
OMIM RCV000002452 SCV000022610 pathogenic Usher syndrome type 2A 2004-04-01 no assertion criteria provided literature only
Counsyl RCV000002452 SCV001132312 likely pathogenic Usher syndrome type 2A 2019-01-24 no assertion criteria provided clinical testing
Counsyl RCV000984234 SCV001132313 likely pathogenic Retinitis pigmentosa 39 2019-01-24 no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000412796 SCV001922732 likely pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000412796 SCV001959112 likely pathogenic not provided no assertion criteria provided clinical testing
Natera, Inc. RCV000002452 SCV002094005 pathogenic Usher syndrome type 2A 2021-01-29 no assertion criteria provided clinical testing

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