ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.6683T>A (p.Val2228Glu)

gnomAD frequency: 0.00019  dbSNP: rs117461552
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Total submissions: 7
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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 RCV000041892 SCV000065588 benign not specified 2012-05-07 criteria provided, single submitter clinical testing Val2228Glu in Exon 35 of USH2A: This variant is not expected to have clinical si gnificance because it has been identified in 4.2% (5/120) of chromosomes from a population in the dbSNP database (http://www.ncbi.nlm.nih.gov/projects/SNP; rs11 7461552).
Invitae RCV000923089 SCV001068550 benign not provided 2024-01-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000041892 SCV002500338 likely benign not specified 2022-03-11 criteria provided, single submitter clinical testing Variant summary: USH2A c.6683T>A (p.Val2228Glu) results in a non-conservative amino acid change located in the Fibronectin type III domain (IPR003961) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00051 in 251052 control chromosomes, predominantly at a frequency of 0.0069 within the East Asian subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in USH2A causing Usher Syndrome (0.00051 vs 0.011), allowing no conclusion about variant significance. c.6683T>A has been reported in the literature with conflicting interpretations (VUS/Likely Benign) along with other variants in the USH2A gene (phase not specified) in cohorts of individuals undergoing whole exome sequencing (WES) for genetic evaluation of Retinal Degeneration (RD) and in particular with Retinitis Pigmentosa (example, Ma_2021). These report(s) do not provide unequivocal conclusions about association of the variant with Usher Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Genome-Nilou Lab RCV003450878 SCV004181628 likely benign Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001826600 SCV004181629 likely benign Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Dept Of Ophthalmology, Nagoya University RCV003888403 SCV004707963 benign Retinal dystrophy 2023-10-01 criteria provided, single submitter research
Natera, Inc. RCV001826600 SCV002090875 likely benign Usher syndrome type 2A 2020-05-03 no assertion criteria provided clinical testing

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