ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.10554+16T>C

gnomAD frequency: 0.00024  dbSNP: rs370288739
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001698357 SCV000534185 likely benign not provided 2018-04-17 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000423560 SCV001448520 benign not specified 2020-11-09 criteria provided, single submitter clinical testing Variant summary: RYR2 c.10554+16T>C alters a non-conserved 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 0.00019 in 247366 control chromosomes, predominantly at a frequency of 0.00033 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 9.6-fold the estimated maximal expected allele frequency for a pathogenic variant in RYR2 causing Catecholaminergic Polymorphic Ventricular Tachycardia phenotype (3.4e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.10554+16T>C in individuals affected with Catecholaminergic Polymorphic Ventricular Tachycardia 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, citing the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV003103994 SCV002392660 likely benign Catecholaminergic polymorphic ventricular tachycardia 1 2024-01-24 criteria provided, single submitter clinical testing
Clinical Genetics, Academic Medical Center RCV000423560 SCV001924820 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001698357 SCV001932588 likely benign not provided no assertion criteria provided clinical testing

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