chr5-177513767-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM1PM5PP2PP3BS2_Supporting
The NM_016222.4(DDX41):c.1016G>A(p.Arg339His) variant causes a missense change. The variant allele was found at a frequency of 0.0000539 in 1,613,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R339C) has been classified as Uncertain significance.
Frequency
Consequence
NM_016222.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DDX41 | NM_016222.4 | c.1016G>A | p.Arg339His | missense_variant | 10/17 | ENST00000330503.12 | |
DDX41 | NM_001321732.2 | c.638G>A | p.Arg213His | missense_variant | 9/16 | ||
DDX41 | NM_001321830.2 | c.638G>A | p.Arg213His | missense_variant | 10/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DDX41 | ENST00000330503.12 | c.1016G>A | p.Arg339His | missense_variant | 10/17 | 1 | NM_016222.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251270Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135892
GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461604Hom.: 0 Cov.: 36 AF XY: 0.0000440 AC XY: 32AN XY: 727102
GnomAD4 genome AF: 0.0000592 AC: 9AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74320
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 339 of the DDX41 protein (p.Arg339His). This variant is present in population databases (rs774698335, gnomAD 0.02%). This missense change has been observed in individual(s) with myeloproliferative/lymphoproliferative neoplasms (PMID: 31713024, 35671390, 37199125). ClinVar contains an entry for this variant (Variation ID: 434921). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 29, 2023 | 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; This variant is associated with the following publications: (PMID: 34183866, 36542832, 31713024, 27721487, 35671390, 36672294, 36036093) - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 07, 2016 | - - |
DDX41-related hematologic malignancy predisposition syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 22, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at