Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001066177 | SCV001231179 | likely pathogenic | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2019-03-07 | 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CC2D2A are known to be pathogenic (PMID: 19777577). 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. This variant has not been reported in the literature in individuals with CC2D2A-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 25 of the CC2D2A gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |