Submissions for variant NM_001323289.2(CDKL5):c.2046+3A>G

dbSNP: rs751000827

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV003328439	SCV004035166	likely benign	CDKL5 disorder	2023-08-23	reviewed by expert panel	curation	The c.2046+3A>G variant in CDKL5 is present in 1 female and 1 male individual(s) in gnomAD (0.001097) (not sufficient to meet BS1 criteria). Splice prediction analysis, using multiple computational tools does not suggest an impact to splicing (BP4). The c.2046+3A>G variant is found in a patient with an alternate molecular basis of disease (internal database) (BP5). In summary, the c.2046+3A>G variant in CDKL5 is classified as likely benign based on the ACMG/AMP criteria (BP4, BP5).
GeneDx	RCV000606213	SCV000716410	likely benign	not specified	2017-03-01	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV002531179	SCV003604607	uncertain significance	Inborn genetic diseases	2022-02-15	criteria provided, single submitter	clinical testing	The c.2046+3A>G intronic alteration consists of a A to G substitution 3 nucleotides after exon 13 (coding exon 12) of the CDKL5 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.