Submissions for variant NM_001142800.2(EYS):c.9209T>C (p.Ile3070Thr)

gnomAD frequency: 0.00013  dbSNP: rs183589498

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000938878	SCV001084704	benign	not provided	2024-01-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000132637	SCV001326600	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003330509	SCV004037881	uncertain significance	not specified	2023-08-04	criteria provided, single submitter	clinical testing	Variant summary: EYS c.9209T>C (p.Ile3070Thr) results in a non-conservative amino acid change located in the Laminin G domain (IPR001791) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00032 in 157018 control chromosomes, predominantly at a frequency of 0.0039 within the East Asian subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1.14-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 East Asian origin. c.9209T>C has been reported in the literature in East Asian individuals affected with Retinitis Pigmentosa without cosegregation information (Hosono_2012, Oishi_2014, Miyata_2017, Koyanagi_2019, Dan_2020, Ma_2021). Some patients had other variants without a confirmed phase, including a pathogenic variant. 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. The following publications have been ascertained in the context of this evaluation (PMID: 22363543, 25324289, 27658286, 31213501, 31960602, 33691693). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as benign, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Dept Of Ophthalmology, Nagoya University	RCV003888558	SCV004707377	likely benign	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Department of Ophthalmology and Visual Sciences Kyoto University	RCV000132637	SCV000172588	pathogenic	Retinitis pigmentosa		no assertion criteria provided	not provided	Converted during submission to Pathogenic.