Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetic Services Laboratory, |
RCV001815218 | SCV002064122 | likely pathogenic | not provided | 2015-12-04 | criteria provided, single submitter | clinical testing | This sequence change affects the canonical acceptor splice site of intron 5 and is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated DDX41 protein with potentially abnormal function. This sequence change appears to be novel and does not appear to have been described in patients or the normal population databases. This sequence change is predicted to be likely pathogenic, however functional studies have not been performed to prove this conclusively. This patient is a carrier of this likely pathogenic sequence change in DDX41. Germline mutations in DDX41 are associated with the development of hereditary myelodysplastic syndrome and acute myeloid leukemia. Our interpretation is based on the current understanding of the genetics of DDX41-related myeloid neoplasms. |
| Invitae | RCV001815218 | SCV003439313 | likely pathogenic | not provided | 2023-03-16 | 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. Studies have shown that disruption of this splice site results in skipping of exon 6 and/or partial retention of intron 6 and introduces a premature termination codon (PMID: 26712909). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 224636). Disruption of this splice site has been observed in individual(s) with DDX41-related conditions (PMID: 26712909, 32054657). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change affects a splice site in intron 5 of the DDX41 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. |
| OMIM | RCV000210273 | SCV000266346 | risk factor | DDX41-related hematologic malignancy predisposition syndrome | 2023-03-16 | no assertion criteria provided | literature only |