ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.8472_8483del (p.2827_2830SGSR[4]) (rs397516967)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038107 SCV000061773 likely benign not specified 2013-02-11 criteria provided, single submitter clinical testing Ser2843_Arg2846del in exon 24 of DSP: This variant is not expected to have clini cal significance because it has been identified in 1.45% (62/4266) of African Am erican chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). This in-frame deletion of four amino acids occurs within a section of repeating amino acids, which can result from several different DNA deletions, and is present in mammals (dolphin, opossum, and platy pus) and other evolutionarily distant species.
Invitae RCV000550762 SCV000641355 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2018-10-31 criteria provided, single submitter clinical testing This sequence change deletes 12 nucleotides from exon 24 of the DSP mRNA (c.8472_8483delGTCCCGCTCCGG). This leads to the deletion of 4 amino acid residues in the DSP protein (p.Ser2843_Arg2846del) but otherwise preserves the integrity of the reading frame. The frequency data for this variant (rs780838070) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with a DSP-related disease but it has been reported in one control individual (PMID:21636032). ClinVar contains an entry for this variant (Variation ID: 44970). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Color RCV000777971 SCV000914074 uncertain significance Cardiomyopathy 2018-10-04 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant deletes 12 nucleotides from exon 24 of the DSP gene, resulting in in-frame deletion of 4 amino acids. This variant occurs in five mammalian species and all of non-mammalian vertebrates, suggesting that this variant may be functionally tolerated. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been reported in an individual affected with dilated cardiomyopathy in a public database (www.cardiodb.org). This variant has also been identified in 20/274794 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Although there is no indication this variant causes disease, available evidence is insufficient to rule out the pathogenicity of this variant conclusively.

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