ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.2151A>G (p.Arg717=)

dbSNP: rs886043453
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel RCV003235178 SCV003933695 likely pathogenic CDKL5 disorder 2023-04-14 reviewed by expert panel curation The p.Arg717= variant in CDKL5 occurs in the de novo state (biological parentage confirmed) in an individual (Invitae internal database )(PS2). The p.Arg717= variant in CDKL5 occurs in the de novo state (biological parentage unconfirmed) in an individual (GeneDx internal database). The p.Arg717= variant has been observed in at least 2 individuals with neurological disease (Invitae and GeneDx internal database). The p.Arg717= variant in CDKL5 is absent from gnomAD (PM2_supporting). In summary, the p.Arg717= variant in CDKL5 is classified as likely pathogenic for a CDKL5-related disorder based on the ACMG/AMP criteria (PS2, PS4_supporting, PM2_supporting).
Eurofins Ntd Llc (ga) RCV000402438 SCV000340250 uncertain significance not provided 2016-03-25 criteria provided, single submitter clinical testing
Invitae RCV001379966 SCV001577882 likely pathogenic Developmental and epileptic encephalopathy, 2; Angelman syndrome-like 2023-10-03 criteria provided, single submitter clinical testing This sequence change affects codon 717 of the CDKL5 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CDKL5 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of 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: 286706). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
GeneDx RCV000402438 SCV003923649 uncertain significance not provided 2022-11-02 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this variant does not alter splicing; Has not been previously published as pathogenic or benign to our knowledge

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