Submissions for variant NM_001385.3(DPYS):c.350G>A (p.Trp117Ter)

gnomAD frequency: 0.00004  dbSNP: rs371567511

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001763852	SCV002000052	uncertain significance	not provided	2024-02-21	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Has not been previously published as pathogenic or benign in association with DPYS-related dihydropyrimidinase deficiency to our knowledge; This variant is associated with the following publications: (PMID: 36414408)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001763852	SCV003280489	pathogenic	not provided	2022-01-15	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with DPYS-related conditions. This variant is present in population databases (rs371567511, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Trp117*) in the DPYS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DPYS are known to be pathogenic (PMID: 20362666). ClinVar contains an entry for this variant (Variation ID: 1313488). For these reasons, this variant has been classified as Pathogenic.