ClinVar Miner

Submissions for variant NM_001142800.2(EYS):c.9299_9302del (p.Thr3100fs) (rs769824975)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000987720 SCV001137153 pathogenic Retinitis pigmentosa 25 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000987720 SCV001160464 likely pathogenic Retinitis pigmentosa 25 2019-04-18 criteria provided, single submitter clinical testing The EYS c.9299_9302delCTCA; p.Thr3100fs variant (rs769824975) is published in the medical literature in an individual with autosomal recessive retinitis pigmentosa who also carried an additional EYS variant of uncertain significance (Pierrottet 2014). The variant is reported in the general population with an overall allele frequency of 0.004% (8/186008 alleles) in the Genome Aggregation Database. This variant results in a premature termination codon in the last exon of the EYS gene. While this may not lead to nonsense-mediated decay, it is expected to create a truncated EYS protein. Other frameshift variants in this region are described as pathogenic (see link to ClinVar, Hosono 2012). Considering available information, this variant is classified as likely pathogenic. References: Link to EYS in ClinVar: http://www.ncbi.nlm.nih.gov/clinvar/?term=EYS%5Bgene%5D Hosono K et al. Two novel mutations in the EYS gene are possible major causes of autosomal recessive retinitis pigmentosa in the Japanese population. PLoS One. 2012;7(2):e31036. Pierrottet CO et al. Syndromic and non-syndromic forms of retinitis pigmentosa: a comprehensive Italian clinical and molecular study reveals new mutations. Genet Mol Res. 2014 Oct 27;13(4):8815-33.
Invitae RCV001057792 SCV001222305 pathogenic not provided 2020-10-05 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the EYS gene (p.Thr3100Lysfs*26). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 45 amino acids of the EYS protein. This variant is present in population databases (rs769824975, ExAC 0.05%). This variant has been observed in combination with another EYS variant in individuals affected with retinitis pigmentosa (PMID: 25366773, 29550188). This variant disrupts the C-terminus of the EYS protein. Other variant(s) that disrupt this region (p.Val3096Leufs*28) have been determined to be pathogenic (PMID: 24474277, 29550188, 26261414, 20333770, 18976725, 25356976). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001073642 SCV001239193 pathogenic Retinal dystrophy 2019-07-26 criteria provided, single submitter clinical testing

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