Submissions for variant NM_001127222.2(CACNA1A):c.2692G>A (p.Gly898Ser)

gnomAD frequency: 0.00004  dbSNP: rs751726770

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000694253	SCV000822688	likely benign	Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42	2023-12-13	criteria provided, single submitter	clinical testing
GeneDx	RCV000841214	SCV000983172	likely benign	not provided	2020-07-29	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV002267622	SCV002549873	uncertain significance	Migraine, familial hemiplegic, 1	2022-07-18	criteria provided, single submitter	clinical testing	_x000D_ Criteria applied: PP3, BS1
Ambry Genetics	RCV002424647	SCV002743446	likely benign	Inborn genetic diseases	2019-06-24	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.
PreventionGenetics, part of Exact Sciences	RCV003985411	SCV004780864	likely benign	CACNA1A-related disorder	2023-09-05	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).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004702335	SCV005203075	likely benign	not specified	2024-07-09	criteria provided, single submitter	clinical testing	Variant summary: CACNA1A c.2695G>A (p.Gly899Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was detected at a frequency of 0.00011 in 1592736 control chromosomes, suggesting the variant could be benign. To our knowledge, no occurrence of c.2695G>A in individuals affected with Epileptic Encephalopathy, Early Infantile, 42 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 572781). Based on the evidence outlined above, the variant was classified as likely benign.