ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.2436+2T>C (rs774514264)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000420343 SCV000531013 likely pathogenic not provided 2016-08-26 criteria provided, single submitter clinical testing The c.2436+2T>C variant in the DSP gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 17. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.2436+2T>C variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret c.2436+2T>C as a likely pathogenic variant.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000611197 SCV000713317 likely pathogenic Arrhythmogenic right ventricular cardiomyopathy 2019-01-17 criteria provided, single submitter clinical testing The c.2436+2T>C variant in DSP has not been previously reported in the literatur e in individuals with cardiomyopathy, but has been reported by other clinical la boratories in ClinVar (Variation ID: 388661). It has also been identified in 1/6 6720 European chromosomes by the Genome Aggregation Database (gnomAD, http://gno mad.broadinstitute.org/; dbSNP rs774514264). This variant occurs in the invarian t region (+/- 1,2) of the splice consensus sequence and is predicted to cause al tered splicing leading to an abnormal or absent protein, which is common among d isease causing DSP variants. In summary, although additional studies are require d to fully establish its clinical significance, the c.2436+2T>C variant is likel y pathogenic.

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