Submissions for variant NM_016203.4(PRKAG2):c.639C>T (p.Thr213=)

gnomAD frequency: 0.00493  dbSNP: rs140001300

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038952	SCV000062630	benign	not specified	2012-03-16	criteria provided, single submitter	clinical testing	Thr213Thr in exon 4 of PRKAG2: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located near a splice junction, and has been identified in 1.9% (71/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs140001300).
Invitae	RCV000230000	SCV000290214	benign	Lethal congenital glycogen storage disease of heart	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000242637	SCV000318803	benign	Cardiovascular phenotype	2014-12-08	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769249	SCV000900625	benign	Cardiomyopathy	2016-08-19	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000769249	SCV000903380	benign	Cardiomyopathy	2018-03-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000038952	SCV000918091	benign	not specified	2018-08-14	criteria provided, single submitter	clinical testing	Variant summary: PRKAG2 c.639C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0015 in 277086 control chromosomes, predominantly at a frequency of 0.016 within the African subpopulation in the gnomAD database, including 5 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 640-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in PRKAG2 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. A ClinVar submission from another clinical diagnostic laboratory (evaluation after 2014) cites the variant as "benign." Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001668164	SCV001471037	benign	not provided	2022-04-08	criteria provided, single submitter	clinical testing
GeneDx	RCV001668164	SCV001890868	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001668164	SCV004156985	benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	PRKAG2: BP4, BP7, BS1, BS2
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000038952	SCV001740525	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000038952	SCV001924804	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000038952	SCV001952585	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000038952	SCV001964542	benign	not specified		no assertion criteria provided	clinical testing
Cohesion Phenomics	RCV003125871	SCV003803053	benign	Hypertrophic cardiomyopathy	2022-09-29	no assertion criteria provided	clinical testing