ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.6050-15G>A

gnomAD frequency: 0.00006  dbSNP: rs373838930
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000155053 SCV000204737 uncertain significance not specified 2014-12-29 criteria provided, single submitter clinical testing The c.6050-15G>A variant in CDH23 has not been previously reported in individual s with hearing loss but has been identified in 1/8480 of European chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs 373838930). Although this variant has been seen in the general population, its f requency is not high enough to rule out a pathogenic role. This variant is locat ed in the 3' splice region. Computational tools predict that this variant may cr eate a novel splice acceptor site, which would likely cause a frameshift in the protein; however, this information is not predictive enough to determine pathoge nicity. In summary, the clinical significance of the c.6050-15G>A variant is unc ertain.
Blueprint Genetics RCV001075025 SCV001240636 uncertain significance Retinal dystrophy 2018-03-20 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001305819 SCV001495167 pathogenic not provided 2024-11-22 criteria provided, single submitter clinical testing This sequence change falls in intron 46 of the CDH23 gene. It does not directly change the encoded amino acid sequence of the CDH23 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or altered protein product. This variant is present in population databases (rs373838930, gnomAD 0.007%). This variant has been observed in individual(s) with Usher syndrome (PMID: 31546658; internal data). 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: 178309). Studies have shown that this variant results in altered splicing, and produces a non-functional protein and/or introduces a premature termination codon (PMID: 31546658). For these reasons, this variant has been classified as Pathogenic.
DBGen Ocular Genomics RCV001589015 SCV001816059 uncertain significance Usher syndrome type 1D 2021-06-01 criteria provided, single submitter clinical testing
GeneDx RCV001305819 SCV001818094 pathogenic not provided 2021-10-28 criteria provided, single submitter clinical testing Non-canonical splice site variant demonstrated to result in loss-of-function (Valero et al, 2019); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 31130284, 31546658)
Baylor Genetics RCV003474812 SCV004210584 likely pathogenic Pituitary adenoma 5, multiple types 2023-12-22 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005049433 SCV005681806 likely pathogenic Autosomal recessive nonsyndromic hearing loss 12; Usher syndrome type 1D; Pituitary adenoma 5, multiple types 2024-03-08 criteria provided, single submitter clinical testing

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