Submissions for variant NM_000330.4(RS1):c.184+3118C>T

gnomAD frequency: 0.00352  dbSNP: rs139155110

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV002281051	SCV002569936	benign	CDKL5 disorder	2022-08-25	reviewed by expert panel	curation	The allele frequency of the p.Thr1028= variant in CDKL5 is 2.6% in Ashkenazi Jewish 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.Thr1028= variant is observed in at least 2 unaffected individuals (internal database, BS2). In summary, the p.Thr1028= variant in CDKL5 is classified as benign based on the ACMG/AMP criteria (BA1, BS2).
Eurofins Ntd Llc (ga)	RCV000080073	SCV000111968	benign	not specified	2012-12-11	criteria provided, single submitter	clinical testing
GeneDx	RCV000080073	SCV000167651	benign	not specified	2012-03-15	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.
Genetic Services Laboratory, University of Chicago	RCV000080073	SCV000192632	benign	not specified	2013-02-08	criteria provided, single submitter	clinical testing
Invitae	RCV001080945	SCV000287892	benign	Developmental and epileptic encephalopathy, 2; Angelman syndrome-like	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000717699	SCV000848555	likely benign	History of neurodevelopmental disorder	2016-07-27	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
CeGaT Center for Human Genetics Tuebingen	RCV000226052	SCV001155917	uncertain significance	not provided	2016-06-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004537339	SCV004751487	benign	CDKL5-related disorder	2019-04-03	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
RettBASE	RCV000080073	SCV000188377	benign	not specified	2014-05-15	no assertion criteria provided	curation	Silent mutation, often found in cis with c.145+17A>G and c.3003G>A (p.H1001H)
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000606547	SCV000734775	likely benign	Developmental and epileptic encephalopathy, 2		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000080073	SCV001932118	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000080073	SCV001954007	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000226052	SCV001967178	likely benign	not provided		no assertion criteria provided	clinical testing