Submissions for variant NM_001142800.2(EYS):c.8429C>T (p.Thr2810Ile)

gnomAD frequency: 0.00443  dbSNP: rs144513453

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000333936	SCV000341024	benign	not specified	2016-04-13	criteria provided, single submitter	clinical testing
Counsyl	RCV000665932	SCV000790143	likely benign	Retinitis pigmentosa 25	2017-03-06	criteria provided, single submitter	clinical testing
Invitae	RCV000965012	SCV001112269	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001164471	SCV001326603	uncertain significance	Retinitis pigmentosa	2017-04-28	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.
GeneDx	RCV000965012	SCV001944704	benign	not provided	2020-04-08	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 20537394, 20237254)
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV000665932	SCV001984115	benign	Retinitis pigmentosa 25	2020-01-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000333936	SCV002500352	benign	not specified	2022-03-13	criteria provided, single submitter	clinical testing	Variant summary: EYS c.8429C>T (p.Thr2810Ile) results in a non-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 0.00095 in 157414 control chromosomes, predominantly at a frequency of 0.015 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 4.4 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 found primarily in populations of African or African-American origin. Although reported in the literature among EYS variants unlikely to be pathogenic in a cohort of individuals with sporadic or autosomal recessive Retinitis Pigmentosa (example, Audo_2010), to our knowledge, no penetrant association of c.8429C>T in individuals affected with Retinitis Pigmentosa 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 and a predominant consensus as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV000965012	SCV004011676	benign	not provided	2023-05-01	criteria provided, single submitter	clinical testing	EYS: BP4, BS1, BS2
Natera, Inc.	RCV000665932	SCV001453477	likely benign	Retinitis pigmentosa 25	2020-06-17	no assertion criteria provided	clinical testing