ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.8415C>T (p.Ala2805=) (rs377148997)

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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 RCV000150583 SCV000197854 likely benign not specified 2014-07-23 criteria provided, single submitter clinical testing Ala2805Ala in exon 24 of DSP: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 1/4406 African Ameri can chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington. edu/EVS/). Ala2805Ala in exon 24 of DSP (allele frequency = 1/4406) **
GeneDx RCV000150583 SCV000725401 likely benign not specified 2017-06-12 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.
Ambry Genetics RCV000622033 SCV000737841 likely benign Cardiovascular phenotype 2016-12-09 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Color RCV000777985 SCV000914090 likely benign Cardiomyopathy 2018-10-16 criteria provided, single submitter clinical testing
Invitae RCV000864820 SCV001005680 likely benign Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2019-12-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000150583 SCV001363287 benign not specified 2019-04-22 criteria provided, single submitter clinical testing Variant summary: DSP c.8415C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 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 4.8e-05 in 251058 control chromosomes, predominantly at a frequency of 0.00076 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 76 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 a benign polymorphism found primarily in populations of African or African-American origin. The variant is cited in a publication, Patel_2014, with no additional information. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.

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