Submissions for variant NM_016222.4(DDX41):c.1586_1587del (p.Thr529fs)

dbSNP: rs866179648

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV002462887	SCV002756669	pathogenic	not provided	2022-05-17	criteria provided, single submitter	clinical testing	Frameshift 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; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27133828)
Labcorp Genetics (formerly Invitae), Labcorp	RCV002462887	SCV003459874	pathogenic	not provided	2024-08-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Thr529Argfs*12) in the DDX41 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DDX41 are known to be pathogenic (PMID: 26712909, 27133828). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with myelodysplasia (PMID: 27133828). ClinVar contains an entry for this variant (Variation ID: 978204). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003224810	SCV004190941	pathogenic	DDX41-related hematologic malignancy predisposition syndrome	2023-10-09	criteria provided, single submitter	clinical testing
Bone Marrow Failure laboratory, Queen Mary University London	RCV001256170	SCV001432954	likely pathogenic	Acute myeloid leukemia	2020-09-01	no assertion criteria provided	research	This heterozygous frameshift variant of DDX41 was identified in a 58-year old female with AML. Her mother had refractory anemia but has not been tested. Her daughter is an asymptomatic carrier of the variant. The following ACMG/AMP criteria were used: PVS1, PP3.
Clinical Genomics Labs, University Health Network	RCV003224810	SCV003920871	pathogenic	DDX41-related hematologic malignancy predisposition syndrome	2021-02-16	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003393927	SCV004111919	likely pathogenic	DDX41-related disorder	2024-01-16	no assertion criteria provided	clinical testing	The DDX41 c.1586_1587delCA variant is predicted to result in a frameshift and premature protein termination (p.Thr529Argfs*12). This variant was reported in a patient with myelodysplasia with acute myeloid leukaemia (Cardoso et al. 2016. PubMed ID: 27133828). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in DDX41 are expected to be pathogenic. This variant is interpreted as likely pathogenic.