Submissions for variant NM_001374736.1(DST):c.22959+1G>A

dbSNP: rs2094441686

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001241867	SCV001414917	likely pathogenic	Hereditary sensory and autonomic neuropathy type 6; Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency	2022-12-23	criteria provided, single submitter	clinical testing	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. This variant has not been reported in the literature in individuals affected with DST-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 81 of the DST 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 DST are known to be pathogenic (PMID: 22522446, 25059916, 30371979). The DST gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_015548.4, and corresponds to NM_001723.5:c.*151953G>A in the primary transcript.
GeneDx	RCV003332313	SCV004039951	likely pathogenic	not provided	2024-09-04	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); Reported using an alternate transcript (non-epithelial isoform) of the gene; Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease