ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.474+5C>T

gnomAD frequency: 0.00001  dbSNP: rs397517400
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769499 SCV000900894 uncertain significance Cardiomyopathy 2017-03-20 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000769499 SCV001354433 likely benign Cardiomyopathy 2018-11-16 criteria provided, single submitter clinical testing
Invitae RCV001365178 SCV001561436 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2020-06-04 criteria provided, single submitter clinical testing This sequence change falls in intron 4 of the DSC2 gene. It does not directly change the encoded amino acid sequence of the DSC2 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs397517400, ExAC 0.009%). This variant has not been reported in the literature in individuals with DSC2-related disease. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002334430 SCV002638338 likely benign Cardiovascular phenotype 2022-12-06 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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