ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.65G>A (p.Gly22Glu)

dbSNP: rs1602232972
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Total submissions: 3
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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 RCV003235440 SCV003933679 likely pathogenic CDKL5 disorder 2023-04-14 reviewed by expert panel curation The p.Gly22Glu variant occurs in the well-characterized ATP binding region functional domain of the CDKL5 gene (PM1). A pathogenic missense variant (p.Gly22Ala) has been previously identified within this codon which indicates that this residue is critical to the function of the protein ( GeneDx internal database) (PM5). The p.Gly22Glu variant in CDKL5 is absent from gnomAD (PM2_supporting). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). In summary, the p.Gly22Glu variant in CDKL5 is classified as likely pathogenic for a CDKL5-related disorder based on the ACMG/AMP criteria (PM1, PM5, PM2_supporting, PP3).
Mendelics RCV000990475 SCV001141477 likely pathogenic Developmental and epileptic encephalopathy, 2 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV001371944 SCV001568528 uncertain significance Developmental and epileptic encephalopathy, 2; Angelman syndrome-like 2022-06-17 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 803714). This variant has not been reported in the literature in individuals affected with CDKL5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 22 of the CDKL5 protein (p.Gly22Glu).

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