Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000536060 | SCV000639467 | pathogenic | Developmental and epileptic encephalopathy, 2; Angelman syndrome-like | 2023-08-30 | 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. ClinVar contains an entry for this variant (Variation ID: 189568). This variant is also known as IVS +1G>A (Intron 13) and IVS13+1A>G. Disruption of this splice site has been observed in individual(s) with CDKL5-related conditions (PMID: 22982301, 24564546, 31487502, 33436160). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 13 of the CDKL5 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 CDKL5 are known to be pathogenic (PMID: 22872100). |
Rett |
RCV000170015 | SCV000222322 | pathogenic | Atypical Rett syndrome | 2014-03-13 | no assertion criteria provided | curation | Disrupts splice site but effect on transcript uncertain |