Submissions for variant NM_001323289.2(CDKL5):c.1002T>C (p.Ala334=)

gnomAD frequency: 0.00002  dbSNP: rs756986206

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV003165430	SCV003853563	benign	CDKL5 disorder	2023-02-20	reviewed by expert panel	curation	The allele frequency of the p.Ala334= variant in CDKL5 is 0.07448% in South Asian 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.Ala334= variant is observed in at least 1 unaffected individual (Clinvar 210642) (BS2_supporting). The silent p.Ala334= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP7). In summary, the p.Ala334= variant in CDKL5 is classified as Benign based on the ACMG/AMP criteria (BA1, BA2_supporting, BP7).
Genetic Services Laboratory, University of Chicago	RCV000193613	SCV000246935	benign	not specified	2018-08-31	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000725404	SCV000336724	uncertain significance	not provided	2015-11-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002317674	SCV000850246	likely benign	Inborn genetic diseases	2016-10-10	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001078805	SCV001001377	benign	Developmental and epileptic encephalopathy, 2; Angelman syndrome-like	2024-07-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000725404	SCV001945969	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000725404	SCV004700501	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	CDKL5: BP4, BP7, BS2
PreventionGenetics, part of Exact Sciences	RCV004530105	SCV004720966	likely benign	CDKL5-related disorder	2019-03-08	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).