Submissions for variant NM_001142800.2(EYS):c.5743A>G (p.Ser1915Gly)

gnomAD frequency: 0.00124  dbSNP: rs188093810

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000488090	SCV000575479	uncertain significance	not provided	2023-10-01	criteria provided, single submitter	clinical testing	EYS: PM2, BP4
Eurofins Ntd Llc (ga)	RCV000488090	SCV000703598	uncertain significance	not provided	2016-12-19	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000488090	SCV001119418	likely benign	not provided	2024-01-28	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001073586	SCV001239137	uncertain significance	Retinal dystrophy	2019-07-05	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001161045	SCV001322888	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.
GeneDx	RCV000488090	SCV001777819	likely benign	not provided	2020-11-23	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 20333770)
Revvity Omics, Revvity	RCV003144285	SCV003832306	uncertain significance	Retinitis pigmentosa 25	2021-10-14	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001161045	SCV001455498	uncertain significance	Retinitis pigmentosa	2020-01-06	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000488090	SCV001550225	uncertain significance	not provided		no assertion criteria provided	clinical testing	The EYS p.S1915G variant was identified in one heterozygous individual with retinitis pigmentosa (Audo_2010_PMID:20333770). The variant was identified in dbSNP (ID: rs188093810) and ClinVar (classified as uncertain significance by Blueprint Genetics, EGL Genetic Diagnostics, Illumina, and CeGaT Praxis; and as likely benign by Invitae). The variant was identified in control databases in 182 of 155700 chromosomes at a frequency of 0.001169, and was observed at the highest frequency in the European (non-Finnish) population in 149 of 64790 chromosomes (freq: 0.0023) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.S1915 residue is not conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) do not suggest a high likelihood of impact to the protein; however this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a deleterious effect on splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV003932793	SCV004753445	likely benign	EYS-related disorder	2022-07-18	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).