Submissions for variant NM_001943.5(DSG2):c.2001_2001+5del

dbSNP: rs779360113

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001988896	SCV002283825	likely pathogenic	Arrhythmogenic right ventricular dysplasia 10	2021-03-23	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 13 of the DSG2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DSG2 are known to be pathogenic (PMID: 23381804, 23911551). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with DSG2-related conditions. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx	RCV005002758	SCV005628424	likely pathogenic	not provided	2024-07-11	criteria provided, single submitter	clinical testing	Deletion of nucleotides at the exon 13/intron 13 boundary, destroying the canonical splice donor site in intron 13 and predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published in association with arrhythmogenic right ventricular cardiomyopathy to our knowledge; This variant is associated with the following publications: (PMID: 31638835, 33087929)