Starting

Initialising…

IDH2

Final classification

VUS

IDH2 c.430G>C · p.Gly144Arg

IDH2

The IDH2 c.430G>C (p.Gly144Arg; p.G144R) variant has not been reported in ClinVar.

Gene

IDH2

Transcript

NM_002168.2

HGVS · transcript:coding

NM_002168.2:c.430G>C

Consequence

N/A

GRCh38

chr15:90088691 C>G

GRCh37

chr15:90631923 C>G

Basis gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback. ▾

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback.

Classification rationale

PM2 VUS

IDH2 c.430G>C

The IDH2 c.430G>C (p.Gly144Arg; p.G144R) variant has not been reported in ClinVar.¹ This variant is absent from gnomAD v2.1 and gnomAD v4.1, supporting rarity and meeting PM2 because the observed allele frequency of 0 is below the 0.1% threshold.² SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.01, which argues against a splicing mechanism but does not establish the effect of the missense substitution itself.³

PM2 → VUS

1 clinvar ↗

2 gnomad_v2 ↗gnomad_v4 ↗

3 spliceai ↗

Gene diagram · NM_002168.2 · variants mapped to exon structure

IDH2 NM_002168.2

Fetching transcript structure from UCSC…

Applied criteria · 1 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 = 0.01).

SpliceAI ↗

Functional Unknown Oncogenic Effect

OncoKB has not reviewed this specific variant; no variant-level oncogenicity or biological effect is available. Gene-level context: IDH2, a cell metabolism enzyme, is recurrently mutated in various cancer types including acute myeloid leukemia, glioblastoma, and cholangiocarcinoma.

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

7Sources

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

COSMIC

Cancer hotspots