Submissions for variant NM_004415.4(DSP):c.8014C>T (p.Gln2672Ter)

dbSNP: rs1064793890

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000483057	SCV000567280	pathogenic	not provided	2015-07-13	criteria provided, single submitter	clinical testing	The Q2672X variant in the DSP gene has not been reported as a pathogenic variant or as a benignpolymorphism to our knowledge. Q2672X is predicted to result in a truncated protein product due to the lossof the last 200 amino acid residues and therefore cause loss of normal protein function. Other nonsensevariants in the DSP gene have been reported in HGMD in association with cardiomyopathy (Stenson P et al.,2014). Furthermore, the Q2672X variant was not observed in approximately 6,500 individuals of Europeanand African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benignvariant in these populations. In summary, Q2672X in the DSP gene is interpreted as a pathogenic variant.
Invitae	RCV002526544	SCV003197408	pathogenic	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2022-05-14	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln2672*) in the DSP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 200 amino acid(s) of the DSP protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 419466). This variant disrupts a region of the DSP protein in which other variant(s) (p.Glu2728Glyfs*11) have been determined to be pathogenic (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. For these reasons, this variant has been classified as Pathogenic.