Submissions for variant NM_206933.4(USH2A):c.9262G>A (p.Glu3088Lys)

gnomAD frequency: 0.00606  dbSNP: rs56056328

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041944	SCV000065640	benign	not specified	2012-06-26	criteria provided, single submitter	clinical testing	Glu3088Lys in exon 47 of USH2A: This variant is not expected to have clinical si gnificance because it has been identified in 0.7% (47/7020) of European American chromosomes and 0.2% (7/3738) of African American chromosomes from a broad popu lation by the NHLBI Exome sequencing project (http://evs.gs.washington.edu/EVS/; (rs56056328). It addition, it occurrs at an equal frequency in cases and contro ls (McGee 2010; Dreyer 2008).
GeneDx	RCV000585414	SCV000169753	benign	not provided	2019-01-16	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 21909055, 20507924, 26927203, 18273898, 22004887, 21559123, 19683999, 25999674)
Eurofins Ntd Llc (ga)	RCV000041944	SCV000230763	benign	not specified	2015-04-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000585414	SCV000692664	likely benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	USH2A: BP4, BS2
Labcorp Genetics (formerly Invitae), Labcorp	RCV000585414	SCV001111707	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001276959	SCV001750316	benign	Usher syndrome type 2A	2021-07-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000041944	SCV002104150	benign	not specified	2022-02-18	criteria provided, single submitter	clinical testing	Variant summary: USH2A c.9262G>A (p.Glu3088Lys) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0064 in 251272 control chromosomes in the gnomAD database, including 12 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in USH2A causing Usher Syndrome (0.0064 vs 0.011), allowing no conclusion about variant significance. Although this variant has been reported in the literature, to our knowledge, no occurrence of c.9262G>A in individuals affected with Usher Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Six 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 benign.
Fulgent Genetics, Fulgent Genetics	RCV002490584	SCV002802233	likely benign	Usher syndrome type 2A; Retinitis pigmentosa 39	2021-09-09	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000585414	SCV005261755	likely benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV001276959	SCV001463652	likely benign	Usher syndrome type 2A	2020-01-11	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000041944	SCV001925706	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000585414	SCV001973930	likely benign	not provided		no assertion criteria provided	clinical testing