Starting

Initialising…

DDX41

Final classification

VUS

DDX41 c.521A>G · p.Asp174Gly

DDX41

The DDX41 c.521A>G (p.Asp174Gly, p.D174G) variant has not been reported in ClinVar.

Gene

DDX41

Transcript

NM_016222.2

HGVS · transcript:coding

NM_016222.2:c.521A>G

Consequence

N/A

GRCh38

chr5:177515735 T>C

GRCh37

chr5:176942736 T>C

Basis Myeloid Malignancy Specification v1.0.0 lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BP4 supporting; combination = 1 supporting + 1 supporting benign, which maps to VUS because the evidence is conflicting. ▾

Myeloid Malignancy Specification v1.0.0 lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BP4 supporting; combination = 1 supporting + 1 supporting benign, which maps to VUS because the evidence is conflicting.

Classification rationale

PM2 BP4 VUS

DDX41 c.521A>G

The DDX41 c.521A>G (p.Asp174Gly, p.D174G) variant has not been reported in ClinVar.¹ This variant is absent from gnomAD v2.1 and gnomAD v4.1, supporting rarity in the general population.² No reviewed variant-specific functional study was identified for this variant.³ Available computational evidence argues against a damaging effect, with SpliceAI showing no significant splice impact (max delta score 0.14), REVEL 0.124, and BayesDel -0.387301.⁴

PM2 + BP4 → VUS

1 clinvar ↗

2 gnomad_v2 ↗gnomad_v4 ↗

3 oncokb ↗

4 spliceai ↗revelbayesdel

Gene diagram · NM_016222.2 · variants mapped to exon structure

DDX41 NM_016222.2

Fetching transcript structure from UCSC…

Applied criteria · 2 met · select any tile

Met

Not met

Not assessed

N/A

Strength very strong supporting

Pathogenic evidence

PVS

Benign evidence

—

Rationale

Select a criterion.

Sources

Evidence used

Gaps remaining

Rule

—

Research & evidence

Population frequency

gnomAD v4.1

gnomAD v2.1

v4.1

Absent from gnomAD v4.1.

v2.1

Absent from gnomAD v2.1.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v2.1

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v4 ↗ gnomAD v2 ↗

ClinVar

This variant is absent from ClinVar.

ClinVar ↗

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.14). REVEL score = 0.124. BayesDel score = -0.387301.

SpliceAI ↗

Functional Unknown Oncogenic Effect

OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. DDX41, an RNA helicase involved in innate immunity, is recurrently altered by mutation in hematopoietic malignancies.

OncoKB ↗

COSMIC

Cancer hotspots

Somatic evidence Not in COSMIC / hotspots

COSMIC

This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).

Hotspots

This variant does not lie in a statistically significant hotspot.

COSMIC ↗ Hotspots ↗

Sources & reference links

8Sources

CSpec VCEP

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

COSMIC

Cancer hotspots