Submissions for variant NM_001323289.2(CDKL5):c.2465G>A (p.Arg822His)

gnomAD frequency: 0.00004  dbSNP: rs376429571

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV003448302	SCV004176031	likely benign	CDKL5 disorder	2023-02-20	reviewed by expert panel	curation	The p.Arg822His variant in CDKL5 is present in 3 XX and 1 XY individuals in gnomAD v3.1.2 (0.0076%) (not sufficient to meet BS1 criteria). Computational analysis prediction tools suggest that the p.Arg822His variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). The p.Arg822His variant is observed in at least 2 unaffected individuals (internal database-GeneDX) (BS2). In summary, the p.Arg822His variant in CDKL5 is classified as Likely Benign based on the ACMG/AMP criteria (BS2, BP4).
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000420425	SCV000511256	uncertain significance	not provided	2016-11-30	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
Genetic Services Laboratory, University of Chicago	RCV000503048	SCV000593966	uncertain significance	not specified	2016-03-04	criteria provided, single submitter	clinical testing
Invitae	RCV001034449	SCV001197805	likely benign	Developmental and epileptic encephalopathy, 2; Angelman syndrome-like	2023-10-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000420425	SCV002567479	likely benign	not provided	2021-05-07	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Ambry Genetics	RCV002446647	SCV002732332	uncertain significance	Inborn genetic diseases	2019-07-30	criteria provided, single submitter	clinical testing	The p.R822H variant (also known as c.2465G>A), located in coding exon 16 of the CDKL5 gene, results from a G to A substitution at nucleotide position 2465. The arginine at codon 822 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is 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.
PreventionGenetics, part of Exact Sciences	RCV003897838	SCV004708649	likely benign	CDKL5-related condition	2023-08-02	criteria provided, single submitter	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).