Submissions for variant NM_001005242.3(PKP2):c.1379-18A>G

gnomAD frequency: 0.00207  dbSNP: rs113698150

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000127450	SCV000171015	benign	not specified	2014-05-21	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.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000625284	SCV000744701	likely benign	Arrhythmogenic right ventricular dysplasia 9	2015-09-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000127450	SCV001363125	benign	not specified	2019-12-09	criteria provided, single submitter	clinical testing	Variant summary: PKP2 c.1511-18A>G alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 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 0.00045 in 247914 control chromosomes, predominantly at a frequency of 0.0061 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 6-folds over 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 African or African-American origin. To our knowledge, no occurrence of c.1511-18A>G in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission (evaluation after 2014) cites the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000625284	SCV002049464	benign	Arrhythmogenic right ventricular dysplasia 9	2021-11-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000625284	SCV002355222	benign	Arrhythmogenic right ventricular dysplasia 9	2024-01-31	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000127450	SCV001926171	benign	not specified		no assertion criteria provided	clinical testing