ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.1684A>G (p.Thr562Ala)

gnomAD frequency: 0.00001  dbSNP: rs376341076
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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 RCV003159619 SCV003853570 likely benign CDKL5 disorder 2023-03-17 reviewed by expert panel curation The p.Thr562Ala variant in CDKL5 is present in 1 female individual in gnomAD (0.001879%) (not sufficient to meet BS1 criteria). Computational analysis prediction tools suggest that the p.Thr562Ala variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). The p.Thr562Ala variant is observed in at least 2 unaffected individuals (internal database - Ambry Genetics, internal database - Invitae) (BS2). In summary, the p.Thr562Ala variant in CDKL5 is classified as Likely Benign for CDKL5-associated disorder based on the ACMG/AMP criteria (BP4, BS2).
Genetic Services Laboratory, University of Chicago RCV000501261 SCV000593965 uncertain significance not specified 2016-08-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV002316434 SCV000850989 uncertain significance Inborn genetic diseases 2016-05-02 criteria provided, single submitter clinical testing The p.T562A variant (also known as c.1684A>G), located in coding exon 11 of the CDKL5 gene, results from an A to G substitution at nucleotide position 1684. The threonine at codon 562 is replaced by alanine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs376341076. Based on data from the NHLBI Exome Sequencing Project (ESP), the G allele was absent out of 2443 total male alleles studied. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001034114 SCV001197439 likely benign Developmental and epileptic encephalopathy, 2; Angelman syndrome-like 2023-12-09 criteria provided, single submitter clinical testing

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