ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.5975A>G (p.Tyr1992Cys) (rs41303287)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000041873 SCV000065569 benign not specified 2012-04-17 criteria provided, single submitter clinical testing Tyr1992Cys in exon 30 of USH2A: This variant is not expected to have clinical si gnificance because it has been identified in 0.4% (30/7020) of European American chromosomes and 0.2% (9/3738) of African American chromosomes in a broad popula tion by the NHLBI Exome sequencing project (http://evs.gs.washington.edu/EVS/; d bSNP rs41303287).
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000041873 SCV000258290 uncertain significance not specified 2015-02-05 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000041873 SCV000344344 likely benign not specified 2017-07-31 criteria provided, single submitter clinical testing
GeneDx RCV000041873 SCV000515233 likely benign not specified 2017-11-16 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000585540 SCV000605545 likely benign not provided 2017-06-01 criteria provided, single submitter clinical testing The p.Tyr1992Cys variant is listed in the ClinVar database as a variant of uncertain significance and as a benign variant (Variation ID: 48547). This is listed in the Genome Aggregation Database (gnomAD) browser with a frequency in European populations of 0.58% (identified in 888 out of 152,370 chromosomes, including 4 homozygotes), and is considered by at least one research group to be benign based on this high frequency in the general population (Shearer 2014). This variant affects a moderately conserved amino acid considering 12 species (Alamut software v 2.9), and several species of bat have a cysteine at this position, suggesting this change is evolutionary tolerated. Likewise, computational analyses suggest this variant does not have a significant effect on USH2A protein structure/function (SIFT: tolerated, PolyPhen2: benign, and Mutation Taster: polymorphism), nor is it predicted to alter USH2A mRNA splicing (Alamut software v 2.9). Therefore, the p.Tyr1992Cys variant is likely to be benign.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000585540 SCV000692665 likely benign not provided 2017-10-31 criteria provided, single submitter clinical testing
Counsyl RCV000669397 SCV000794145 likely benign Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-09-15 criteria provided, single submitter clinical testing
Invitae RCV000585540 SCV001115902 benign not provided 2019-02-26 criteria provided, single submitter clinical testing
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787924 SCV000926943 uncertain significance Progressive cone dystrophy (without rod involvement) 2018-04-01 no assertion criteria provided research

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