ClinVar Miner

Submissions for variant NM_001142800.2(EYS):c.8834G>A (p.Gly2945Glu)

gnomAD frequency: 0.00004  dbSNP: rs1161453292
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001037096 SCV001200493 pathogenic not provided 2023-12-25 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 2945 of the EYS protein (p.Gly2945Glu). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individuals with retinitis pigmentosa (PMID: 21069908, 21519034, 32036094, 32728228; Invitae). It has also been observed to segregate with disease in related individuals. This variant is also known as Gly2966Glu. ClinVar contains an entry for this variant (Variation ID: 836062). 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.
Blueprint Genetics RCV001073472 SCV001239015 uncertain significance Retinal dystrophy 2019-03-11 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002271614 SCV002555713 uncertain significance not specified 2022-06-07 criteria provided, single submitter clinical testing Variant summary: EYS c.8834G>A (p.Gly2945Glu) results in a non-conservative amino acid change located in the EGF-like domain (IPR000742) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.3e-05 in 156356 control chromosomes (gnomAD). c.8834G>A has been reported in the literature in multiple individuals affected with Retinitis Pigmentosa, however in some cases the second allele reported was not clearly pathogenic (examples: Barragan_2010, Pieras_2011, Weisschuh_2020 and Rodriguez-Munoz_2020) . These data indicate that the variant may to be associated with disease. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant pathogenic (n=1) and VUS (n=2). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Baylor Genetics RCV001827220 SCV004192915 likely pathogenic Retinitis pigmentosa 25 2024-03-26 criteria provided, single submitter clinical testing
Natera, Inc. RCV001827220 SCV002083475 uncertain significance Retinitis pigmentosa 25 2021-03-17 no assertion criteria provided clinical testing

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