Submissions for variant NM_206933.4(USH2A):c.15428G>A (p.Arg5143His)

dbSNP: rs111033435

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041786	SCV000065482	benign	not specified	2012-01-11	criteria provided, single submitter	clinical testing	Arg5143His in exon 71 of USH2A: This variant has been reported in 2/80 individua ls with non-syndromic retinitis pigmentosa (McGee 2010); however, this variant i s not expected to have clinical significance because it has been identified in 5 .1% (188/3738) of African American control chromosomes by the NHBLI Exome sequen cing project (http://evs.gs.washington.edu/EVS; dbSNP rs111033435).
GeneDx	RCV000883059	SCV000169777	benign	not provided	2019-01-16	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27460420, 29024829)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000883059	SCV000605552	benign	not provided	2023-11-06	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000041786	SCV000860033	benign	not specified	2018-03-20	criteria provided, single submitter	clinical testing
Invitae	RCV000883059	SCV001026334	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000883059	SCV001146605	benign	not provided	2019-07-17	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000041786	SCV002104141	benign	not specified	2022-02-22	criteria provided, single submitter	clinical testing	Variant summary: USH2A c.15428G>A (p.Arg5143His) results in a non-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 0.0039 in 251468 control chromosomes (gnomAD), predominantly at a frequency of 0.054 within the African or African-American subpopulation in the gnomAD database, including 31 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 4.87 fold of the estimated maximal expected allele frequency for a pathogenic variant in USH2A causing the Usher Syndrome phenotype (0.011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Six ClinVar submitters have assessed the variant since 2014: all have classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Genome-Nilou Lab	RCV003450821	SCV004182697	benign	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001276137	SCV004182708	benign	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001276137	SCV001461989	benign	Usher syndrome type 2A	2020-09-16	no assertion criteria provided	clinical testing