Submissions for variant NM_206933.4(USH2A):c.6587G>C (p.Ser2196Thr)

gnomAD frequency: 0.04057  dbSNP: rs79444516

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041891	SCV000065587	benign	not specified	2010-07-26	criteria provided, single submitter	clinical testing	Ser2196Thr in exon 34 of USH2A: This variant has now been identified in 4/191 (2 .1%) individuals tested in our laboratory none of whom had a pathogenic USH2A va riant and one case had only conductive hearing loss inconsistent with an USH2A e tiology. In addition, all 4 individuals were Black or Hispanic suggesting this v ariant is very common in this population.
Eurofins Ntd Llc (ga)	RCV000041891	SCV000229759	benign	not specified	2015-02-06	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756879	SCV000884843	benign	not provided	2023-11-28	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000756879	SCV001146617	benign	not provided	2018-11-12	criteria provided, single submitter	clinical testing
Invitae	RCV000756879	SCV001722980	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000756879	SCV001941377	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25262649, 22004887, 19683999, 27884173, 30245029)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000041891	SCV002074298	benign	not specified	2022-01-15	criteria provided, single submitter	clinical testing	Variant summary: USH2A c.6587G>C (p.Ser2196Thr) results in a conservative amino acid change located in the Fibronectin type III domain (IPR003961) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0093 in 250942 control chromosomes, predominantly at a frequency of 0.13 within the African or African-American subpopulation in the gnomAD database, including 127 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 12 fold of the estimated maximal expected allele frequency for a pathogenic variant in USH2A causing Usher Syndrome phenotype (0.011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.6587G>C 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. Based on the evidence outlined above, the variant was classified as benign.
Genome-Nilou Lab	RCV003450877	SCV004181648	benign	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001274252	SCV004181649	benign	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001274252	SCV001458133	benign	Usher syndrome type 2A	2020-09-16	no assertion criteria provided	clinical testing