Submissions for variant NM_001005242.3(PKP2):c.2168-21_2168-20del

dbSNP: rs200266270

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000624998	SCV000743449	benign	Arrhythmogenic right ventricular dysplasia 9	2014-10-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000168936	SCV001362100	benign	not specified	2019-09-02	criteria provided, single submitter	clinical testing	Variant summary: PKP2 c.2300-21_2300-20delGT alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 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 0.016 in 230752 control chromosomes, predominantly at a frequency of 0.046 within the South Asian subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 43 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 South Asian origin. To our knowledge, no occurrence of c.2300-21_2300-20delGT in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000624998	SCV001472337	benign	Arrhythmogenic right ventricular dysplasia 9	2023-11-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000624998	SCV002388203	benign	Arrhythmogenic right ventricular dysplasia 9	2024-02-01	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000168936	SCV000220026	likely benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000168936	SCV001924822	benign	not specified		no assertion criteria provided	clinical testing