ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.4211+2T>G (rs753832779)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667757 SCV000792257 likely pathogenic Usher syndrome, type 1F 2017-06-13 criteria provided, single submitter clinical testing
Invitae RCV000793173 SCV000932514 likely pathogenic not provided 2018-11-09 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 31 of the PCDH15 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs753832779, ExAC 0.02%). This variant has not been reported in the literature in individuals with PCDH15-related disease. ClinVar contains an entry for this variant (Variation ID: 552486). 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PCDH15 are known to be pathogenic (PMID: 11398101, 11487575, 14570705). 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.

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