Submissions for variant NM_001943.5(DSG2):c.2533del (p.Lys844_Ile845insTer)

dbSNP: rs1375081885

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000702405	SCV000831258	pathogenic	Arrhythmogenic right ventricular dysplasia 10	2018-06-12	criteria provided, single submitter	clinical testing	This sequence change results in a premature translational stop signal in the DSG2 gene (p.Ile845*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 274 amino acids of the DSG2 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DSG2-related disease. A different truncation (p.Glu1020Alafs*18) that lies downstream of this variant has been determined to be pathogenic (PMID: 21397041, 20864495, 23381804). This suggests that deletion of this region of the DSG2 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	RCV000702405	SCV000839952	likely pathogenic	Arrhythmogenic right ventricular dysplasia 10	2018-04-25	criteria provided, single submitter	clinical testing	DSG2: c.2533delA (p.ILE845*) This c.2533delA (p.ILE845*) variant in the DSG2 gene has not been reported previously nor observed in general population according to gnomad database. This variant is predicted to cause loss of function of normal protein through mRNA decay or producing a truncated protein, which is a known disease mechanism for this gene. Based on current evidences, this c.2533delA (p.ILE845*) variant in the DSG2 gene is classified as likely pathogenic