Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001237427 | SCV001410186 | pathogenic | Cerebral cavernous malformation 2 | 2019-07-29 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 6 of the CCM2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CCM2 are known to be pathogenic (PMID: 2468908, 14624391, 17160895, 18300272). 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. Disruption of this splice site has been observed in individuals affected with cerebral cavernous malformations (Invitae). This variant is not present in population databases (ExAC no frequency). |