ClinVar Miner

Submissions for variant NM_016203.4(PRKAG2):c.472G>A (p.Gly158Ser)

gnomAD frequency: 0.00054  dbSNP: rs727504512
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000155655 SCV000205364 likely benign not specified 2013-04-17 criteria provided, single submitter clinical testing Gly158Ser in exon 4 of PRKAG2: This variant is not expected to have clinical sig nificance due to a lack of evolutionary conservation. Of note, multiple mammals (including mouse, rat, squirrel, and rabbit) have a serine (Ser) at this positio n despite high nearby amino acid conservation. In addition, computational analys es (AlignGVGD, PolyPhen2, SIFT) do not suggest a high likelihood of impact to th e protein and the variant is located outside the CBS domain region where all pat hogenic PRKAG2 variants have been identified to date (Oliveira 2003).
GeneDx RCV001719977 SCV000208936 likely benign not provided 2021-02-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000457420 SCV000561809 likely benign Lethal congenital glycogen storage disease of heart 2025-01-13 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000155655 SCV000918093 likely benign not specified 2017-12-11 criteria provided, single submitter clinical testing Variant summary: The PRKAG2 c.472G>A (p.Gly158Ser) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 141/277028 control chromosomes in gnomAD (1 homozygote) at a frequency of 0.000509, which is approximately 20 times the estimated maximal expected allele frequency of a pathogenic PRKAG2 variant (0.000025), suggesting this variant is likely a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. In addition, multiple clincial labs classified this variant as likely benign and one other lab classified it as VUS, all without evidence for independent evaluation. Taken together, this variant is classified as likely benign.
Color Diagnostics, LLC DBA Color Health RCV001177593 SCV001341830 likely benign Cardiomyopathy 2018-12-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV002336332 SCV002635921 likely benign Cardiovascular phenotype 2019-04-26 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.

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