ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.6829+3A>G (rs780258798)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000606653 SCV000713282 uncertain significance not specified 2017-05-25 criteria provided, single submitter clinical testing The c.6829+3A>G variant in CDH23 has not been previously reported in individuals with hearing loss or Usher syndrome, but has been identified in 14/32810 chromo somes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.o rg/; dbSNP rs780258798). Although this variant has been seen in the general popu lation, its frequency is not high enough to rule out a pathogenic role. This var iant is located in the 5' splice region. Computational tools do not suggest an i mpact to splicing. However, this information is not predictive enough to rule ou t pathogenicity. In summary, the clinical significance of the c.6829+3A>G varian t is uncertain.
Invitae RCV001045178 SCV001209015 uncertain significance not provided 2019-12-12 criteria provided, single submitter clinical testing This sequence change falls in intron 49 of the CDH23 gene. It does not directly change the encoded amino acid sequence of the CDH23 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs780258798, ExAC 0.01%). This variant has not been reported in the literature in individuals with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 505846). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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