ClinVar Miner

Submissions for variant NM_001142800.2(EYS):c.8111T>G (p.Leu2704Ter)

gnomAD frequency: 0.00003  dbSNP: rs779983752
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000779514 SCV000916158 likely pathogenic Retinitis pigmentosa 2019-01-09 criteria provided, single submitter clinical testing The EYS c.8111T>G (p.Leu2704Ter) stop-gained variant has been reported in one study and identified in two compound heterozygotes with retinitis pigmentosa (Sengillo et al. 2018). One of the individuals had a second frameshift variant and the other had a second missense variant. Control data are unavailable for this variant which is reported at a frequency of 0.000080 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the evidence, the p.Leu2704Ter variant is classified as likely pathogenic for autosomal recessive retinitis pigmentosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000791712 SCV000930972 pathogenic not provided 2024-01-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu2704*) in the EYS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EYS are known to be pathogenic (PMID: 18836446, 20333770). This variant is present in population databases (rs779983752, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 29550188). ClinVar contains an entry for this variant (Variation ID: 632492). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001074431 SCV001240015 likely pathogenic Retinal dystrophy 2017-02-15 criteria provided, single submitter clinical testing
GeneDx RCV000791712 SCV002817676 likely pathogenic not provided 2022-06-27 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 34598035, 29550188)
Baylor Genetics RCV003467306 SCV004192956 pathogenic Retinitis pigmentosa 25 2023-08-24 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000779514 SCV004241060 pathogenic Retinitis pigmentosa 2023-12-13 criteria provided, single submitter clinical testing Variant summary: EYS c.8111T>G (p.Leu2704X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 3.9e-05 in 153424 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.8111T>G has been reported in the literature in individuals affected with retinal dystrophy (e.g., Sengillo_2018). These data indicate that the variant is very likely to be associated with disease. The following publication was ascertained in the context of this evaluation (PMID: 29550188). Five submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Natera, Inc. RCV000779514 SCV001453305 pathogenic Retinitis pigmentosa 2020-09-16 no assertion criteria provided clinical testing

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