Submissions for variant NM_001323289.2(CDKL5):c.825+5G>A

dbSNP: rs1555951149

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000519715	SCV000621595	uncertain significance	not provided	2017-10-16	criteria provided, single submitter	clinical testing	The c.825+5G>A variant in the CDKL5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.825+5G>A variant is not observed in large population cohorts (Lek et al., 2016). However, in silico analyses, including splice predictors and evolutionary conservation, support that this variant does not alter protein structure/function. However, in the absence of RNA/functional studies, the actual effect of c.825+5G>A is unknown. We interpret c.825+5G>A as a variant of uncertain significance.
Invitae	RCV001235948	SCV001408657	uncertain significance	Developmental and epileptic encephalopathy, 2; Angelman syndrome-like	2022-01-13	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 10 of the CDKL5 gene. It does not directly change the encoded amino acid sequence of the CDKL5 protein. It affects a nucleotide within the consensus splice site. This variant has not been reported in the literature in individuals affected with CDKL5-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 452763).