Submissions for variant NM_001142800.2(EYS):c.6050G>T (p.Gly2017Val)

gnomAD frequency: 0.00002  dbSNP: rs868349465

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001034750	SCV001198047	pathogenic	not provided	2023-12-29	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2017 of the EYS protein (p.Gly2017Val). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 21069908, 31074760, 32728228). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 560459). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on EYS protein function. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV002499195	SCV002811862	likely pathogenic	Retinitis pigmentosa 25	2024-06-17	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV002499195	SCV003832397	likely pathogenic	Retinitis pigmentosa 25	2023-11-08	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV002499195	SCV004192854	likely pathogenic	Retinitis pigmentosa 25	2024-03-19	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV002499195	SCV004808261	likely pathogenic	Retinitis pigmentosa 25	2024-03-29	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004817916	SCV005073046	likely pathogenic	Retinal dystrophy	2022-01-01	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000678568	SCV000804647	pathogenic	Macular dystrophy	2016-09-01	no assertion criteria provided	clinical testing
Faculty of Health Sciences, Beirut Arab University	RCV001257882	SCV001434633	pathogenic	Autosomal recessive retinitis pigmentosa	2012-10-26	no assertion criteria provided	literature only
PreventionGenetics, part of Exact Sciences	RCV004751660	SCV005342549	likely pathogenic	EYS-related disorder	2024-06-03	no assertion criteria provided	clinical testing	The EYS c.6050G>T variant is predicted to result in the amino acid substitution p.Gly2017Val. This variant has been reported in the homozygous state or with a second EYS variant in individuals with retinitis pigmentosa (see for examples, Barragán et al. 2010. PubMed ID: 21069908; Messchaert et al. 2017. PubMed ID: 29159838; Cundy et al. 2020. PubMed ID: 32728228; Panneman et al. 2023. PubMed ID: 36819107). It has also been reported with a second EYS variant in an individual with macular dystrophy (Pierrache et al. 2019. PubMed ID: 31074760). This variant is reported in 0.012% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. Given the evidence, we interpret this variant as likely pathogenic.