Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001958834 | SCV002243324 | pathogenic | Developmental and epileptic encephalopathy, 1; Autosomal recessive spinocerebellar ataxia 12 | 2021-06-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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 individual(s) with autosomal recessive epileptic encephalopathy with cerebellar atrophy (PMID: 30853297). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 5 of the WWOX gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in WWOX are known to be pathogenic (PMID: 24456803, 25411445). |