ClinVar Miner

Submissions for variant NM_016222.4(DDX41):c.1574G>A (p.Arg525His)

dbSNP: rs869312828
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002288840 SCV002578413 uncertain significance not provided 2022-05-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies are inconclusive, some suggesting that this variant by itself does not significantly affect protein translation or localization, some suggesting a possible hypomorphic effect, and some suggesting inhibition of proliferation and ATPase activity (Kadono et al., 2016; Lewinsohn et al., 2016; Chlon et al., 2021); Observed in the germline of an individual with myelodysplastic syndrome in published literature (Lewinsohn et al., 2016); Common second hit somatic variant observed in many affected individuals who also have a DDX41 germline variant (Polprasert et al., 2015); This variant is associated with the following publications: (PMID: 26712909, 34473945, 31713024, 34349893, 27174803, 33929502, 33836623, 33585199, 33692849, 27721487, 25920683)
Labcorp Genetics (formerly Invitae), Labcorp RCV002288840 SCV003439299 uncertain significance not provided 2022-06-28 criteria provided, single submitter clinical testing Experimental studies have shown that this missense change affects DDX41 function (PMID: 25920683, 27174803). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 224634). This missense change has been observed in individual(s) with leukemia (PMID: 26712909). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 525 of the DDX41 protein (p.Arg525His).
OMIM RCV000210250 SCV000266344 risk factor DDX41-related hematologic malignancy predisposition syndrome 2023-03-16 no assertion criteria provided literature only
GeneReviews RCV000210250 SCV001999939 not provided DDX41-related hematologic malignancy predisposition syndrome no assertion provided literature only Most common somatic variant; also reported in the germline [Kadono et al 2016, Lewinsohn et al 2016, Cheah et al 2017]
Clinical Genomics Labs, University Health Network RCV000210250 SCV003920866 pathogenic DDX41-related hematologic malignancy predisposition syndrome 2022-02-17 no assertion criteria provided clinical testing

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