Submissions for variant NM_000117.3(EMD):c.466G>A (p.Gly156Ser)

gnomAD frequency: 0.00078  dbSNP: rs144594695

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001721139	SCV000235900	benign	not provided	2020-03-26	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000183440	SCV000337756	likely benign	not specified	2015-12-08	criteria provided, single submitter	clinical testing
Invitae	RCV000467850	SCV000560795	likely benign	X-linked Emery-Dreifuss muscular dystrophy	2024-01-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000183440	SCV000917316	likely benign	not specified	2018-11-19	criteria provided, single submitter	clinical testing	Variant summary: EMD c.466G>A (p.Gly156Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00032 in 199875 control chromosomes, including 20 hemizygotes, in the gnomAD database. The variant was predominantly observed within the African subpopulation, at a frequency of 0.0032 (including 18 hemizygotes), and although this frequency is somewhat lower than expected for a pathogenic variant in EMD causing Cardiomyopathy (0.0032 vs 0.0071), the large number of hemizygotes among the controls suggests that the variant still might be a benign polymorphism. To our knowledge, no occurrence of c.466G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Ambry Genetics	RCV002336466	SCV002638127	benign	Cardiovascular phenotype	2018-12-13	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Natera, Inc.	RCV001833106	SCV002084692	benign	Emery-Dreifuss muscular dystrophy	2019-12-13	no assertion criteria provided	clinical testing