ClinVar Miner

Submissions for variant NM_001142800.2(EYS):c.7492G>C (p.Ala2498Pro)

gnomAD frequency: 0.00004  dbSNP: rs1311193836
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001248690 SCV001422195 pathogenic not provided 2024-01-10 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 2498 of the EYS protein (p.Ala2498Pro). This variant is present in population databases (no rsID available, gnomAD 0.07%). This missense change has been observed in individual(s) with cone-rod dystrophy and/or retinitis pigmentosa (PMID: 25356976, 30804660, 33090715). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 972618). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003323834 SCV004029270 pathogenic Retinitis pigmentosa 2023-07-27 criteria provided, single submitter clinical testing Variant summary: EYS c.7492G>C (p.Ala2498Pro) 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 damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.5e-05 in 156982 control chromosomes. c.7492G>C has been reported in the literature in multiple individuals affected with Retinitis Pigmentosa (Gao_2022, Huang_2014) . These data indicate that the variant is very likely to be associated with disease. 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: 34689181, 25356976). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as pathogenic, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV001830049 SCV004192863 pathogenic Retinitis pigmentosa 25 2024-03-22 criteria provided, single submitter clinical testing
Dept Of Ophthalmology, Nagoya University RCV003887974 SCV004707436 pathogenic Retinal dystrophy 2023-10-01 criteria provided, single submitter research
Natera, Inc. RCV001830049 SCV002083517 uncertain significance Retinitis pigmentosa 25 2021-04-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.