ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.7248del (p.Phe2416fs)

dbSNP: rs730880024
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498058 SCV000589541 pathogenic not provided 2017-06-27 criteria provided, single submitter clinical testing The c.7248delT variant in the DSP gene has been reported previously in the homozygous state in an individual with acantholytic epidermolysis bullosa (Hobbs et al., 2010). The c.7248delT variant causes a frameshift starting with codon Phenylalanine 2416, changes this amino acid to a Leucine residue, and creates a premature Stop codon at position 14 of the new reading frame, denoted p.Phe2416LeufsX14. This variant is predicted to cause loss of normal protein function through protein truncation. The c.7248delT variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.7248delT as a pathogenic variant.
Invitae RCV002515042 SCV003439322 pathogenic Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2023-09-21 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the DSP protein in which other variant(s) (p.Glu2728Glyfs*11) have been determined to be pathogenic (PMID: 21859740, 28527814; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 180181). This premature translational stop signal has been observed in individual(s) with autosomal recessive lethal acantholytic epidermolysis bullosa and/or clinical features of autosomal dominant arrhythmogenic cardiomyopathy (PMID: 20613772; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe2416Leufs*14) in the DSP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 456 amino acid(s) of the DSP protein.
OMIM RCV000157033 SCV000206761 pathogenic Lethal acantholytic epidermolysis bullosa 2010-11-01 no assertion criteria provided literature only

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