Submissions for variant NM_001142800.2(EYS):c.5510G>C (p.Trp1837Ser)

gnomAD frequency: 0.00333  dbSNP: rs199689193

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000176624	SCV000228312	likely benign	not specified	2014-11-19	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000504628	SCV000464418	uncertain significance	Retinitis pigmentosa	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Counsyl	RCV000665978	SCV000790202	likely benign	Retinitis pigmentosa 25	2017-03-17	criteria provided, single submitter	clinical testing
Invitae	RCV000963176	SCV001110313	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000665978	SCV001159163	likely benign	Retinitis pigmentosa 25	2020-04-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000963176	SCV001865806	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24265693)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000176624	SCV002555712	likely benign	not specified	2022-06-07	criteria provided, single submitter	clinical testing	Variant summary: EYS c.5510G>C (p.Trp1837Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.004 in 153716 control chromosomes in the gnomAD database, including 6 homozygotes. The observed variant frequency is approximately 1.17 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 benign. c.5510G>C has been reported in the literature in individuals affected with Retinitis Pigmentosa, however it is often observed in the heterozygous state without a variant reported in the second allele and in several studies the variant was considered to be a polymorphism (example Audo_2010, Eisenberger_2013, Wang_2014, Perez-Carro_2016). These reports do not provide unequivocal conclusions about association of the variant with Retinitis Pigmentosa. Six ClinVar submitters have provided assessments for this variant after 2014. Two classified the variant as benign, three as likely benign, and one as VUS. Based on the evidence outlined above, the variant was classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV000963176	SCV003917074	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	EYS: BP4, BS2
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504628	SCV000599155	likely benign	Retinitis pigmentosa	2015-01-01	no assertion criteria provided	research
Natera, Inc.	RCV000504628	SCV001459613	benign	Retinitis pigmentosa	2020-01-10	no assertion criteria provided	clinical testing