ClinVar Miner

Submissions for variant NM_001242897.2(DEPDC5):c.562+1G>A (rs1057524233)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000433181 SCV000534956 likely pathogenic not provided 2017-01-06 criteria provided, single submitter clinical testing The c.562+1G>A variant in the DEPDC5 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 9. 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.562+1G>A variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.562+1G>A as a likely pathogenic variant.
Invitae RCV001038460 SCV001201929 pathogenic Familial focal epilepsy with variable foci 2019-07-18 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 9 of the DEPDC5 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in a family affected with epilepsy and/or intellectual disability (PMID: 30525188) and has been reported to segregate with nocturnal epilepsy in a family (Invitae). ClinVar contains an entry for this variant (Variation ID: 391802). 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 DEPDC5 are known to be pathogenic (PMID: 23542697, 23542701). For these reasons, this variant has been classified as Pathogenic.

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