ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.156G>A (p.Lys52=) (rs201210997)

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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,Partners HealthCare Personalized Medicine RCV000038169 SCV000061835 benign not specified 2016-08-14 criteria provided, single submitter clinical testing p.Lys52Lys in exon 1 of PKP2: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 1% (78/8192) of Lati no chromosomes, including 1 homozygote, by the Exome Aggregation Consortium (ExA C,; dbSNP rs201210997).
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000229030 SCV000267450 likely benign Arrhythmogenic right ventricular cardiomyopathy, type 9 2016-03-18 criteria provided, single submitter reference population
Invitae RCV000229030 SCV000288594 benign Arrhythmogenic right ventricular cardiomyopathy, type 9 2018-01-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV000247345 SCV000319199 benign Cardiovascular phenotype 2014-12-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene
Color RCV000771825 SCV000904532 benign Cardiomyopathy 2018-03-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000038169 SCV000920003 benign not specified 2018-12-03 criteria provided, single submitter clinical testing Variant summary: PKP2 c.156G>A 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 0.0013 in 242920 control chromosomes, predominantly at a frequency of 0.0078 within the Latino subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 7.25 fold of the estimated maximal expected allele frequency for a pathogenic variant in PKP2 causing Cardiomyopathy phenotype (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. c.156G>A has been reported in the literature in individuals affected with Cardiomyopathy (Wu_2009). These report(s) do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has 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 benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.

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