ClinVar Miner

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

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
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 (; 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

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.