Submissions for variant NM_001142800.2(EYS):c.6119T>A (p.Val2040Asp)

gnomAD frequency: 0.00166  dbSNP: rs201580493

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000177451	SCV000168382	benign	not specified	2011-12-16	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)	RCV000177451	SCV000229310	likely benign	not specified	2014-06-17	criteria provided, single submitter	clinical testing
Invitae	RCV000882506	SCV001025747	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001003019	SCV001321379	uncertain significance	Retinitis pigmentosa	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Baylor Genetics	RCV001292621	SCV001481212	uncertain significance	Retinitis pigmentosa 25	2019-10-11	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Pars Genome Lab	RCV001292621	SCV001652878	likely benign	Retinitis pigmentosa 25	2021-05-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000177451	SCV002500083	likely benign	not specified	2023-03-15	criteria provided, single submitter	clinical testing	Variant summary: EYS c.6119T>A (p.Val2040Asp) results in a non-conservative amino acid change located in the first laminin G repeat domain (IPR001791) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0017 in 152886 control chromosomes, predominantly at a frequency of 0.0038 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 1.11 fold of the estimated maximal expected allele frequency for a pathogenic variant in EYS causing Retinitis Pigmentosa phenotype (0.0034), strongly suggesting that the variant is a benign polymorphism. c.6119T>A has been reported in the literature in individuals affected with Retinitis Pigmentosa (Audo_2010, Barragan_2010, Sharon_2020, Dinero_2020). These reports do not provide unequivocal conclusions about association of the variant with Retinitis Pigmentosa. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five other ClinVar submitters have assessed the variant since 2014: two classified the variant as of uncertain significance, two as likely benign, and one as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV000882506	SCV004157477	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	EYS: BP4
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001003019	SCV001161074	likely pathogenic	Retinitis pigmentosa	2019-06-23	no assertion criteria provided	research