Submissions for variant NM_206933.4(USH2A):c.7130A>G (p.Asn2377Ser)

gnomAD frequency: 0.00378  dbSNP: rs111033394

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041903	SCV000065599	benign	not specified	2012-04-27	criteria provided, single submitter	clinical testing	Asn2377Ser in exon 38 of USH2A: This variant is not expected to have clinical si gnificance because it has been identified in 0.5% (35/7016) of European American chromosomes and 0.1% (7/3738) of African American chromosomes in a broad popula tion by the NHLBI Exome sequencing project (http://evs.gs.washington.edu/EVS/; d bSNP rs111033394).
Eurofins Ntd Llc (ga)	RCV000041903	SCV000229930	benign	not specified	2014-12-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000512740	SCV000515234	benign	not provided	2018-06-12	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25910913, 26927203, 22004887)
CeGaT Center for Human Genetics Tuebingen	RCV000512740	SCV000608523	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	USH2A: BP4, BS2
Counsyl	RCV000665008	SCV000789061	likely benign	Usher syndrome type 2A; Retinitis pigmentosa 39	2016-12-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000512740	SCV001054669	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000512740	SCV001474082	benign	not provided	2021-08-20	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000041903	SCV002500135	benign	not specified	2022-03-05	criteria provided, single submitter	clinical testing	Variant summary: USH2A c.7130A>G (p.Asn2377Ser) results in a conservative amino acid change in 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 0.0039 in 250098 control chromosomes in the gnomAD database, including 8 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in USH2A causing Usher Syndrome (0.0039 vs 0.011), allowing no conclusion about variant significance. Although reported in the literature, to our knowledge, no penetrant association of c.7130A>G 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.
Genome-Nilou Lab	RCV003450883	SCV004181555	likely benign	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001271989	SCV004181556	likely benign	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000512740	SCV005261762	likely benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV001271989	SCV001453617	likely benign	Usher syndrome type 2A	2020-06-12	no assertion criteria provided	clinical testing