ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.972G>A (p.Ala324=) (rs142636176)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038233 SCV000061901 benign not specified 2013-01-13 criteria provided, single submitter clinical testing Ala324Ala in exon 3 of PKP2: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 0.6% (25/4406) of Afr ican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs142636176).
GeneDx RCV000038233 SCV000236180 benign not specified 2014-09-09 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000464866 SCV000557336 benign Arrhythmogenic right ventricular cardiomyopathy, type 9 2018-01-01 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770422 SCV000901865 benign Cardiomyopathy 2017-04-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000038233 SCV000918017 benign not specified 2018-06-25 criteria provided, single submitter clinical testing Variant summary: PKP2 c.972G>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 observed variant frequency within African control individuals in the gnomAD database is approximately 13.5 fold of the estimated maximal expected allele frequency for a pathogenic variant in PKP2 causing Arrhythmia phenotype (0.00043), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.972G>A in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.

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