ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.3220G>A (p.Asp1074Asn)

gnomAD frequency: 0.00001  dbSNP: rs750452808
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001758188 SCV001985726 uncertain significance not provided 2019-10-28 criteria provided, single submitter clinical testing Predicted to destroy the natural splice donor site; adjacent exon 27 is in frame; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 27743452, 27460420)
Labcorp Genetics (formerly Invitae), Labcorp RCV001758188 SCV004294746 likely pathogenic not provided 2023-09-01 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies and prediction algorithms are not available or were not evaluated, and the effect of this variant on mRNA splicing is currently unknown. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1303895). This missense change has been observed in individual(s) with deafness and/or Usher syndrome (PMID: 27460420, 27743452, 35020051). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs750452808, gnomAD 0.003%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1074 of the CDH23 protein (p.Asp1074Asn). This variant also falls at the last nucleotide of exon 27, which is part of the consensus splice site for this exon.

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