Submissions for variant NM_206933.4(USH2A):c.15377T>C (p.Ile5126Thr)

gnomAD frequency: 0.02380  dbSNP: rs111033266

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041785	SCV000065481	benign	not specified	2012-02-20	criteria provided, single submitter	clinical testing	Ile5126Thr in exon 71 of USH2A: This variant is not expected to have clinical si gnificance because this residue is not conserved across species and computationa l analyses do not suggest a high likelihood of clinical significance. In additio n, this variant been identified in 3% (161/5018 chromosomes) of a broad populati on (dbSNP rs111033266).
GeneDx	RCV000041785	SCV000169776	benign	not specified	2012-03-21	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Eurofins Ntd Llc (ga)	RCV000041785	SCV000232400	benign	not specified	2015-05-20	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000971261	SCV001118893	benign	not provided	2025-02-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000041785	SCV002074297	benign	not specified	2022-01-15	criteria provided, single submitter	clinical testing	Variant summary: USH2A c.15377T>C (p.Ile5126Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0062 in 251464 control chromosomes, predominantly at a frequency of 0.075 within the African or African-American subpopulation in the gnomAD database, including 45 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 6.76 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. Three 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.
Fulgent Genetics, Fulgent Genetics	RCV002504924	SCV002805317	likely benign	Usher syndrome type 2A; Retinitis pigmentosa 39	2022-05-06	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000971261	SCV003800311	benign	not provided	2022-09-13	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003450820	SCV004182764	likely benign	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001276138	SCV004182775	likely benign	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000971261	SCV005287588	benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV001276138	SCV001461990	benign	Usher syndrome type 2A	2020-09-16	no assertion criteria provided	clinical testing