Submissions for variant NM_001035.3(RYR2):c.7342+16A>G

gnomAD frequency: 0.00698  dbSNP: rs76678214

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000250520	SCV000306073	benign	not specified		criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000250520	SCV001360977	benign	not specified	2019-08-12	criteria provided, single submitter	clinical testing	Variant summary: RYR2 c.7342+16A>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 0.0048 in 249216 control chromosomes, predominantly at a frequency of 0.023 within the East Asian and African-American subpopulations in the gnomAD database, including 9 homozygotes. The observed variant frequency within East Asian and African-American control individuals in the gnomAD database is approximately 383-folds over the estimated maximal expected allele frequency for a pathogenic variant in RYR2 causing Arrhythmia phenotype (6e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian and African-American origins. To our knowledge, no occurrence of c.7342+16A>G in individuals affected with Arrhythmia 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	RCV001610603	SCV001473988	benign	not provided	2020-03-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001610603	SCV001840613	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Invitae	RCV002518600	SCV002408187	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-02-01	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000250520	SCV001918760	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000250520	SCV001972103	benign	not specified		no assertion criteria provided	clinical testing