ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.8209-3A>G (rs376788358)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036795 SCV000060450 likely benign not specified 2019-09-24 criteria provided, single submitter clinical testing The c.8209-3G>A variant in RYR2 is classified as likely benign because it has been identified in 0.15% (34/21760) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant is located in the 3' splice region. Although a subset of computational tools predict a possible splicing impact, this information is not predictive enough to support pathogenicity in the absence of additional data. ACMG/AMP Criteria applied: BA1, PP3.
GeneDx RCV000036795 SCV000235153 uncertain significance not specified 2017-03-09 criteria provided, single submitter clinical testing The c.8209-3 A>G variant in the RYR2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. In silico splice prediction algorithms demonstrate that c.8209-3 A>G may result in loss of the natural splice acceptor site of intron 54, which may cause abnormal gene splicing. This may lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. However, the majority of disease causing mutations in the RYR2 gene are missense changes. The NHLBI ESP Exome Variant Server reports c.8209-3 A>G was observed at a low frequency (4/3596) of alleles from individuals of African American background. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY,POSTMORTEM panel(s).
Ambry Genetics RCV000621356 SCV000736332 likely benign Cardiovascular phenotype 2019-04-03 criteria provided, single submitter clinical testing Subpopulation frequency in support of benign classification
Invitae RCV000866921 SCV001008090 likely benign Catecholaminergic polymorphic ventricular tachycardia 2020-11-13 criteria provided, single submitter clinical testing
Color Health, Inc RCV001175859 SCV001339638 likely benign Cardiomyopathy 2019-09-23 criteria provided, single submitter clinical testing
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000678751 SCV000804927 uncertain significance Dilated cardiomyopathy with left ventricular noncompaction 2015-10-01 no assertion criteria provided clinical testing

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