ClinVar Miner

Submissions for variant NM_001142800.2(EYS):c.3443+1G>T

gnomAD frequency: 0.00022  dbSNP: rs373441420
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000724528 SCV000227912 pathogenic not provided 2015-01-20 criteria provided, single submitter clinical testing
Counsyl RCV000176281 SCV000798238 likely pathogenic Retinitis pigmentosa 25 2018-03-06 criteria provided, single submitter clinical testing
Invitae RCV000724528 SCV001234831 pathogenic not provided 2023-12-26 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 22 of the EYS gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in EYS are known to be pathogenic (PMID: 18836446, 20333770). This variant is present in population databases (rs373441420, gnomAD 0.06%). Disruption of this splice site has been observed in individuals with retinal disease (PMID: 20237254, 29550188; Invitae). ClinVar contains an entry for this variant (Variation ID: 195665). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001074850 SCV001240451 pathogenic Retinal dystrophy 2019-07-24 criteria provided, single submitter clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear RCV000176281 SCV001573647 pathogenic Retinitis pigmentosa 25 2021-04-08 criteria provided, single submitter research The EYS c.3443+1G>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PP3. Based on this evidence we have classified this variant as Pathogenic.
GeneDx RCV000724528 SCV001812529 pathogenic not provided 2019-10-08 criteria provided, single submitter clinical testing Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 29550188, 25097241, 26667666)
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001274886 SCV001950264 pathogenic Retinitis pigmentosa 2021-04-01 criteria provided, single submitter curation The c.3443+1G>T variant in EYS was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PP3. Based on this evidence we have classified this variant as Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab.
Revvity Omics, Revvity RCV000176281 SCV002022259 pathogenic Retinitis pigmentosa 25 2021-06-25 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003398889 SCV004111794 pathogenic EYS-related condition 2023-03-01 criteria provided, single submitter clinical testing The EYS c.3443+1G>T variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been reported in the homozygous and compound heterozygous states in individual with retinitis pigmentosa (Wang et al. 2014. PubMed ID: 25097241; Ge et al. 2015. PubMed ID: 26667666; Sengillo et al. 2018. PubMed ID: 29550188). This variant is reported in 0.057% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-65523270-C-A). Variants that disrupt the consensus splice donor site in EYS are expected to be pathogenic, and this variant has been classified as pathogenic or likely pathogenic by multiple independent submitters to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/195665). Given the evidence, we interpret c.3443+1G>T as pathogenic.
Baylor Genetics RCV000176281 SCV004192894 pathogenic Retinitis pigmentosa 25 2023-10-11 criteria provided, single submitter clinical testing
Natera, Inc. RCV001274886 SCV001459436 likely pathogenic Retinitis pigmentosa 2020-09-16 no assertion criteria provided clinical testing

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