ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.2276+1G>A

dbSNP: rs1602292181
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV001004660 SCV001164109 pathogenic Developmental and epileptic encephalopathy, 2 2015-10-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001860565 SCV002292246 likely pathogenic Developmental and epileptic encephalopathy, 2; Angelman syndrome-like 2021-11-10 criteria provided, single submitter clinical testing 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. 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: 813729). Disruption of this splice site has been observed in individual(s) with clinical features of CDKL5-related conditions (PMID: 22872100). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 15 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).
Centre for Population Genomics, CPG RCV004726774 SCV005335186 pathogenic CDKL5 disorder 2024-09-16 criteria provided, single submitter curation This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as pathogenic. At least the following criteria are met: Predicted to result in loss of function, and LOF is a known mechanism of disease (PVS1). This variant is absent from gnomAD (PM2_Supporting). Has been observed in at least 2 individuals with phenotypes consistent with CDKL5 disorder (PS4_Supporting, PMID: 22872100, ClinVar Variation ID: 813729).

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