ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.1455_1460del (p.Ala486_Lys487del)

dbSNP: rs587783114
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel RCV002260621 SCV002540700 benign CDKL5 disorder 2022-02-18 reviewed by expert panel curation The allele frequency of the p.Ala486_Lys487del variant in CDKL5 is 0.03% in Latino/Admixed American sub population in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). The p.Ala486_Lys487del variant is observed in 1 unaffected individual (RettBASE, PMID 22867051) (BS2_supporting). In summary, the p.Ala486_Lys487del variant in CDKL5 is classified as benign based on the ACMG/AMP criteria applied (BA1, BS2_supporting).
GeneDx RCV000766721 SCV000191009 uncertain significance not provided 2016-06-19 criteria provided, single submitter clinical testing The c.1455_1460delGGCCAA variant in the CDKL5 gene has been previously identified in a female patient with developmental delay, absent speech, seizures, and difficulty walking; however, it was classified by the authors as a variant of unknown significance because it was inherited from her unaffected mother and both the patient and her mother had normal X-inactivation studies (Maortua et al., 2012). The variant results in an in-frame deletion of two amino acids. Therefore, based on the currently available information, it is unclear whether c.1455_1460delGGCCAA is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001405417 SCV001607338 likely benign Developmental and epileptic encephalopathy, 2; Angelman syndrome-like 2025-01-23 criteria provided, single submitter clinical testing
Centre for Population Genomics, CPG RCV002260621 SCV005894722 benign CDKL5 disorder 2024-09-13 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 benign. At least the following criteria are met: The allele frequency of this variant in at least one population in gnomAD is higher than the 0.03% threshold defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders VCEP 3.0 (BA1).
RettBASE RCV000169974 SCV000222278 likely benign not specified 2014-05-09 no assertion criteria provided curation Found in unaffected female
PreventionGenetics, part of Exact Sciences RCV004544327 SCV004778327 likely benign CDKL5-related disorder 2022-08-09 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.