ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.1266+6G>T (rs73375345)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000037987 SCV000061653 likely benign not specified 2012-01-10 criteria provided, single submitter clinical testing 1266+6G>T in intron 10 of DSP: This variant is not expected to have clinical sig nificance because it has been identified in 0.5% (19/3738) of African American c hromosomes from a broad, though clinically unspecified population (NHLBI Exome S equencing Project; This variant is also liste d in dbSNP (rs73375345). 1266+6G>T in intron 10 of DSP (rs73375345, NHLBI Exome Seq Project; 0.5%, 19/3738)
GeneDx RCV000037987 SCV000168255 benign not specified 2014-03-12 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000467421 SCV000555769 benign Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2017-12-11 criteria provided, single submitter clinical testing
Color RCV000771844 SCV000904558 benign Cardiomyopathy 2018-10-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000037987 SCV000919292 benign not specified 2018-02-05 criteria provided, single submitter clinical testing Variant summary: DSP c.1266+6G>T 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. 3/5 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 0.00065 in 276288 control chromosomes in gnomAD. The observed variant frequency is approximately 64.79 fold of the estimated maximal expected allele frequency for a pathogenic variant in DSP causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. c.1266+6G>T has been reported in the literature in one individual with DCM (Pugh_2014), and was considered likley benign by the authors. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.

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