Submissions for variant NM_001323289.2(CDKL5):c.744+1G>A

dbSNP: rs1925705674

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001070396	SCV001235623	pathogenic	Developmental and epileptic encephalopathy, 2; Angelman syndrome-like	2020-06-01	criteria provided, single submitter	clinical testing	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 CDKL5 are known to be pathogenic (PMID: 22872100). 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 been observed in individual(s) with CDKL5-related conditions (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 863429). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 9 of the CDKL5 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics	RCV001089714	SCV001245199	pathogenic	Developmental and epileptic encephalopathy, 2	2020-02-14	criteria provided, single submitter	clinical testing