IDH2c.514A>GPathogenic

Print report

Variant interpretation report

IDH2 c.514A>G, p.(Arg172Gly)

NM_002168.3:c.514A>G NP_002159.2:p.(Arg172Gly) View identifiers

Classification

Pathogenic

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is pathogenic. Select a step to read what it means.

Pathogenic.A pathogenic classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About IDH2

No gene-level summary was recorded for this case.

Key facts

Evidence used: 1 strong (pathogenic) · 2 moderate (pathogenic) · 2 supporting (pathogenic)
Expert rules: Not recorded
Other laboratories (ClinVar): 1 Likely pathogenic
Pipeline record: 1 Aug 2026 · version 7.0.4

Evidence considered

View criteria

Applied evidence criteria

PS3 (strong): Two independent publications directly tested the exact IDH2 R172G variant in cell line models, demonstrating loss of wild-type enzymatic activity and gain of neomorphic oncogenic function. PMID:21641335 showed that IDH2 R172G diminishes NADPH production and alters cellular proliferation. PMID:22309944 showed that IDH2 R172G overexpression induces HIF-1α upregulation and β-catenin nuclear accumulation. The neomorphic gain-of-function (2-hydroxyglutarate production) is a well-established consequence of IDH2 R172 mutations, corroborated by PMID:21326614 for the broader R172 class.
PM1 (moderate): Variant is located at arginine 172, the catalytic active-site residue in IDH2 (analogous to IDH1 R132). This is a well-established critical functional domain in the enzyme active site and a statistically significant mutational hotspot (cancerhotspots.org). ClinVar submission SCV005902248 independently cites PM1 for this variant.
PM2 (moderate): Variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada v1.0 (allele frequency = 0.0). Meets PM2 threshold of <0.1% for non-VCEP generic ACMG application.
PP3 (supporting): REVEL score 0.669 predicts a deleterious effect on protein function (>0.5 threshold). SpliceAI predicts no splice impact (max delta 0.03). Multiple in silico tools support a deleterious effect, though BayesDel (0.383) is borderline. Overall evidence supports a damaging in silico prediction.
PP5 (supporting): Reported as Likely pathogenic in ClinVar (Variation ID: 376439) by Clinical Genomics Laboratory, Washington University in St. Louis (SCV005902248, criteria provided, single submitter). A reputable clinical laboratory has classified this variant as likely pathogenic with supporting criteria; while a single-submitter submission without expert panel review carries less weight than a 3-star classification, the criteria-provided submission from a clinical diagnostic laboratory satisfies PP5 at supporting strength under generic ACMG.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.

01The reasoning

How it was classified

The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 5 Benign evidence criteria: 0

Pathogenic criteria applied · 5

PS3Strong

PS3 · strong

Two independent publications directly tested the exact IDH2 R172G variant in cell line models, demonstrating loss of wild-type enzymatic activity and gain of neomorphic oncogenic function. PMID:21641335 showed that IDH2 R172G diminishes NADPH production and alters cellular proliferation. PMID:22309944 showed that IDH2 R172G overexpression induces HIF-1α upregulation and β-catenin nuclear accumulation. The neomorphic gain-of-function (2-hydroxyglutarate production) is a well-established consequence of IDH2 R172 mutations, corroborated by PMID:21326614 for the broader R172 class.

PM1Moderate

PM1 · moderate

Variant is located at arginine 172, the catalytic active-site residue in IDH2 (analogous to IDH1 R132). This is a well-established critical functional domain in the enzyme active site and a statistically significant mutational hotspot (cancerhotspots.org). ClinVar submission SCV005902248 independently cites PM1 for this variant.

PM2Moderate

PM2 · moderate

Variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada v1.0 (allele frequency = 0.0). Meets PM2 threshold of <0.1% for non-VCEP generic ACMG application.

PP3Supporting

PP3 · supporting

REVEL score 0.669 predicts a deleterious effect on protein function (>0.5 threshold). SpliceAI predicts no splice impact (max delta 0.03). Multiple in silico tools support a deleterious effect, though BayesDel (0.383) is borderline. Overall evidence supports a damaging in silico prediction.

PP5Supporting

PP5 · supporting

Reported as Likely pathogenic in ClinVar (Variation ID: 376439) by Clinical Genomics Laboratory, Washington University in St. Louis (SCV005902248, criteria provided, single submitter). A reputable clinical laboratory has classified this variant as likely pathogenic with supporting criteria; while a single-submitter submission without expert panel review carries less weight than a 3-star classification, the criteria-provided submission from a clinical diagnostic laboratory satisfies PP5 at supporting strength under generic ACMG.

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

Recorded classification: Pathogenic

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PS3 strong, PM1 moderate, PM2 moderate, PP3 supporting, PP5 supporting; combination = 1 strong + 2 moderate + 2 supporting, which maps to Pathogenic.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

gnomAD v4.1

gnomAD v2.1

Population frequency

Not recorded

gnomAD v4.1 allele counts were not recorded for this variant.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

Applied · PM2 →

gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗

SpliceAI score

0.030 maximum delta

Recorded SpliceAI maximum delta score: 0.030. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · PP3 → SpliceAI ↗

ClinVar submissions

1 reported laboratory submissions

1 Likely pathogenic. ClinVar API review status: criteria provided, single submitter.

Applied · PP5 → ClinVar ↗

Functional evidence

Statement recorded

OncoKB identified variant-specific curated literature and context relevant to functional review; curated oncogenicity label: Likely Oncogenic.

Applied · PS3 → OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

48 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV57468989, n = 48 times).

Cancer Hotspots

This variant lies in a statistically significant hotspot.

Context only

COSMIC ↗Cancer Hotspots ↗

For specialists

Technical detail

ACMG/AMP criteria under Not recorded, with the data and sources behind each one.

29 criteria with recorded statuses: 5 met · 18 not met · 0 not assessed · 6 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM3 PM4 PM5 PM6 PP1 PP2 PP3 PP4 PP5 PS5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP3 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

PS3 (strong): Two independent publications (PMID:21641335, PMID:22309944) directly tested the exact IDH2 R172G variant, demonstrating loss of wild-type enzymatic activity and gain of neomorphic 2-hydroxyglutarate production.

PM1 (moderate): Variant is located at arginine 172, the catalytic active-site residue in IDH2 and a statistically significant mutational hotspot (cancerhotspots.org).

PM2 (moderate): Variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada (allele frequency = 0.0).

PP3 (supporting): REVEL score 0.669 predicts a deleterious effect on protein function.

PP5 (supporting): Reported as Likely pathogenic in ClinVar by a clinical diagnostic laboratory with criteria provided (Variation ID: 376439).

Overall classification: Pathogenic. The combination of 1 strong criterion (PS3), 2 moderate criteria (PM1, PM2), and 2 supporting criteria (PP3, PP5) satisfies the generic ACMG/AMP 2015 pathogenic threshold (1 Strong + 2 Moderate + 2 Supporting).

Met · 5

PS3 StrongTwo independent publications directly tested the exact IDH2 R172G variant in cell line models, demonstrating loss of wild-type enzymatic activity and gain of neomorphic oncogenic function. PMID:21641335 showed that IDH2 R172G diminishes NADPH production and alters cellular proliferation. PMID:22309944 showed that IDH2 R172G overexpression induces HIF-1α upregulation and β-catenin nuclear accumulation. The neomorphic gain-of-function (2-hydroxyglutarate production) is a well-established consequence of IDH2 R172 mutations, corroborated by PMID:21326614 for the broader R172 class. Details ▾Hide ▴

Evidence considered

PMID:21641335: Site-directed mutagenesis of IDH2 R172G expressed in rat C6 glioma cells
diminished wild-type IDH2 enzymatic activity (NADPH production)
promoted cell proliferation
increased sensitivity to chemotherapy agents.
PMID:22309944: IDH2 R172G overexpression in C6 glioma cells induced nuclear accumulation of β-catenin
up-regulation of HIF-1α signaling
and increased tumor invasion and chemo-resistance marker expression.
ClinVar submission SCV005902248 also cites PS3 for this variant based on functional studies.

Still missing

Functional data derived from rat glioma (C6) and human oligodendroglioma (HOG) cell lines in a somatic cancer context
no germline-specific functional studies available.

Sources

PMID:21641335 ↗PMID:22309944 ↗

PM1 ModerateVariant is located at arginine 172, the catalytic active-site residue in IDH2 (analogous to IDH1 R132). This is a well-established critical functional domain in the enzyme active site and a statistically significant mutational hotspot (cancerhotspots.org). ClinVar submission SCV005902248 independently cites PM1 for this variant. Details ▾Hide ▴

Evidence considered

cancerhotspots.org identifies R172 as a statistically significant mutational hotspot.
R172 is the catalytic arginine residue in the IDH2 active site
analogous to IDH1 R132
the most commonly mutated residue in IDH1-driven cancers.
ClinVar submission SCV005902248 applies PM1: variant resides within the small domain of IDH2 defined as a critical functional domain.

Sources

clinvar ↗PMID:21326614 ↗

PM2 ModerateVariant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada v1.0 (allele frequency = 0.0). Meets PM2 threshold of <0.1% for non-VCEP generic ACMG application. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1 (exomes).
Absent from gnomAD v4.1 (exomes).
Absent from gnomAD-Canada v1.0 (genomes).

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

PP3 SupportingREVEL score 0.669 predicts a deleterious effect on protein function (>0.5 threshold). SpliceAI predicts no splice impact (max delta 0.03). Multiple in silico tools support a deleterious effect, though BayesDel (0.383) is borderline. Overall evidence supports a damaging in silico prediction. Details ▾Hide ▴

Evidence considered

REVEL score: 0.669 (deleterious
>0.5 threshold).
BayesDel score: 0.383 (borderline).
SpliceAI max delta: 0.03 (no predicted splice impact).

Still missing

REVEL verified against PMID:36413997
BayesDel not independently verified.

Sources

revelspliceai ↗bayesdel

PP5 SupportingReported as Likely pathogenic in ClinVar (Variation ID: 376439) by Clinical Genomics Laboratory, Washington University in St. Louis (SCV005902248, criteria provided, single submitter). A reputable clinical laboratory has classified this variant as likely pathogenic with supporting criteria; while a single-submitter submission without expert panel review carries less weight than a 3-star classification, the criteria-provided submission from a clinical diagnostic laboratory satisfies PP5 at supporting strength under generic ACMG. Details ▾Hide ▴

Evidence considered

ClinVar Variation ID: 376439
classification: Likely pathogenic.
Submitter: Clinical Genomics Laboratory
Washington University in St. Louis.
Review status: criteria provided
single submitter.
Submission cites PM1 and PS3 criteria.

Still missing

Single submitter (1-star)
no expert panel review. Strength could be upgraded if additional clinical laboratories corroborate.

Sources

clinvar ↗

Not met · 18 · evaluated, threshold not reached

PS1 No evidence of a different nucleotide change at c.514 resulting in the same p.Arg172Gly amino acid substitution. PS1 requires co-location with a known pathogenic variant causing the identical amino acid change via a different nucleotide substitution. Details ▾Hide ▴

Still missing

No alternate nucleotide changes at codon 172 producing p.Arg172Gly identified in case evidence.

PS2 No evidence of confirmed de novo occurrence with both maternity and paternity confirmed. Details ▾Hide ▴

Still missing

No de novo testing data available.

PS4 No case-control data comparing variant prevalence in affected individuals versus the general population. COSMIC reports 48 somatic cancer occurrences, but these are not suitable for germline PS4 case-control analysis. Details ▾Hide ▴

Evidence considered

COSMIC reports 48 somatic occurrences (COSV57468989)
but somatic data do not constitute germline case-control evidence.

Still missing

No germline case-control or cohort prevalence data available.

PM5 While other pathogenic missense changes at codon 172 are known (R172K, R172M in gliomas; R172W in AML), no same-residue comparator variants with germline pathogenic classification were confirmed in the case evidence. The automated PM5 candidate search returned no qualifying candidates. Literature evidence for other R172 substitutions exists only in somatic cancer context. Details ▾Hide ▴

Evidence considered

PMID:21326614 and PMID:20171147 document R172K and R172M as pathogenic in somatic cancer.
No germline pathogenic classification for other R172 variants confirmed in ClinVar for this case.

Still missing

Other R172 substitutions (R172K
R172M
R172W) lack confirmed germline pathogenic classification in current evidence.

PM6 No de novo observation data available. PM6 requires assumed de novo occurrence without confirmation of paternity and maternity. Details ▾Hide ▴

Still missing

No de novo testing or trio data available.

PP1 No segregation data available. PP1 requires co-segregation with disease in multiple affected family members. Details ▾Hide ▴

Still missing

No family segregation data available.

PP2 HCI prior scores are not available for IDH2. Insufficient data to establish that missense variants are a common mechanism of disease for this gene in a germline context. PP2 requires a gene with a low rate of benign missense variation where missense variants are a common disease mechanism. Details ▾Hide ▴

Evidence considered

HCI prior not found for IDH2 (gene not supported).

Still missing

No gene-level missense constraint metrics (HCI prior
Z-score
pLI) available.

PP4 No phenotype specificity data available for this variant in a germline context. PP4 requires the variant to be found in a patient whose phenotype or family history is highly specific for the disease. Details ▾Hide ▴

Still missing

No patient phenotype or clinical specificity data available for germline context.

BA1 Variant is absent from gnomAD. Does not meet BA1 threshold of >1% (or >5%) allele frequency in population databases. Details ▾Hide ▴

Evidence considered

Allele frequency = 0.0 in all gnomAD datasets.

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 Variant is absent from gnomAD. Does not meet BS1 threshold of >0.3% allele frequency for non-VCEP generic ACMG application. Details ▾Hide ▴

Evidence considered

Allele frequency = 0.0 in all gnomAD datasets.

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS2 No observations in homozygous state in population controls. BS2 requires observation in a healthy adult in a homozygous state for a fully penetrant dominant disorder. Details ▾Hide ▴

Still missing

No homozygous observations in population databases.

BS3 Functional studies demonstrate a deleterious effect: loss of wild-type enzymatic activity and gain of neomorphic 2-hydroxyglutarate production (PMID:21641335, PMID:22309944). These findings are inconsistent with a benign interpretation; BS3 requires well-established in vitro or in vivo functional studies showing no damaging effect. Details ▾Hide ▴

Evidence considered

PMID:21641335: IDH2 R172G diminishes wild-type enzymatic activity and alters cell proliferation.
PMID:22309944: IDH2 R172G induces oncogenic signaling (HIF-1α
β-catenin).
PMID:21326614: IDH2 R172 class mutations produce 2-hydroxyglutarate (neomorphic gain-of-function).

Sources

PMID:21641335 ↗PMID:22309944 ↗PMID:21326614 ↗

BS4 No segregation data available demonstrating non-segregation with disease. BS4 requires lack of segregation in affected family members. Details ▾Hide ▴

Still missing

No family segregation data available.

BP1 IDH2 has known pathogenic missense variants at codon 172 (R172K, R172M in gliomas; R172W in AML). BP1 applies only to genes where missense variants are not a known disease mechanism and the primary mechanism is truncating variants. Details ▾Hide ▴

Evidence considered

Multiple pathogenic missense variants reported at the same residue (R172K
R172M
R172W) in cancer.

Sources

PMID:21326614 ↗

BP2 No observation of this variant in trans with a known pathogenic variant. BP2 requires observation in trans with a pathogenic variant for a fully penetrant dominant disorder. Details ▾Hide ▴

Still missing

No trans-configuration data available.

BP4 REVEL score 0.669 predicts a deleterious effect; multiple computational tools suggest a damaging impact. BP4 requires multiple lines of computational evidence suggesting no impact on gene product. The in silico evidence supports a deleterious prediction. Details ▾Hide ▴

Evidence considered

REVEL: 0.669 (deleterious prediction).
BayesDel: 0.383 (borderline
does not support benign).

Sources

revelbayesdel

BP5 No case identified where this variant is found in an individual with an alternate molecular basis for disease. BP5 requires observation in a case with an established alternate cause. Details ▾Hide ▴

Still missing

No alternate molecular basis data available.

BP6 ClinVar classification for this variant is Likely pathogenic, not benign. BP6 requires a reputable source to report the variant as benign. Details ▾Hide ▴

Evidence considered

ClinVar classification: Likely pathogenic (Variation ID: 376439).

Sources

clinvar ↗

Not applicable · 6· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/AMissense variant (c.514A>G, p.Arg172Gly) does not meet ClinGen SVI PVS1 null-variant criteria: not a nonsense, frameshift, or canonical ±1,2 splice consensus variant. Generic PVS1 framework does not apply. Details ▾Hide ▴

Evidence considered

Per ClinGen SVI PVS1 recommendations (PMC6185798)
missense variants are excluded from default PVS1 null-variant buckets.

Sources

pvs1_generic_framework ↗

PM3 N/ARecessive disorder criterion; IDH2-associated conditions are not recessively inherited. Details ▾Hide ▴

No further detail was recorded.

PM4 N/AProtein length change criterion; variant is a substitution. Details ▾Hide ▴

No further detail was recorded.

BP3 N/AIn-frame deletion/insertion criterion; variant is a substitution. Details ▾Hide ▴

No further detail was recorded.

BP7 N/AThis is a missense variant (c.514A>G, p.Arg172Gly). BP7 applies only to synonymous (silent) variants with no predicted splice impact. Details ▾Hide ▴

Evidence considered

Variant is missense (Arg to Gly)
not synonymous.

PS5 N/APS5 is not a standard ACMG/AMP 2015 criterion. The standard framework does not include this criterion code. Details ▾Hide ▴

No further detail was recorded.

Identifiers

Gene: IDH2
Transcript: NM_002168.3
Coding (HGVS c.): NM_002168.3:c.514A>G
Protein (HGVS p.): NP_002159.2:p.(Arg172Gly)
GRCh38: chr15:90088607 T>C
GRCh37: chr15:90631839 T>C
ClinVar: 376439
COSMIC: COSV57468989

Gene diagram

Every interpreted variant in IDH2, mapped onto the exon structure of NM_002168.3. Select a row to find it on the plot.

IDH2NM_002168.3

Fetching transcript structure from UCSC…

Exons

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Transcript span

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Strand

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Variants mapped

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Source

UCSC ncbiRefSeqCurated

All variants in IDH2 — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 Allele count data not recorded

gnomAD v2.1 Allele count data not recorded

gnomAD-Canada v1.0 Allele count data not recorded

Statements

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat -85 bp

0.030

SpliceAI acceptor gainat -111 bp

0.010

SpliceAI donor lossat -1 bp

0.000

SpliceAI donor gainat -20 bp

0.000

Pangolin splice lossmagnitude shown

-0.010

Pangolin splice gain

0.000

Other predictors

REVEL: 0.669
BayesDel: 0.383

How the predictions were used

Evidence considered

REVEL score: 0.669 (deleterious
>0.5 threshold).
BayesDel score: 0.383 (borderline).
SpliceAI max delta: 0.03 (no predicted splice impact).

Still missing

REVEL verified against PMID:36413997
BayesDel not independently verified.

Sources

revelspliceai ↗bayesdel

Evidence considered

REVEL: 0.669 (deleterious prediction).
BayesDel: 0.383 (borderline
does not support benign).

Sources

revelbayesdel

BP7 N/AThis is a missense variant (c.514A>G, p.Arg172Gly). BP7 applies only to synonymous (silent) variants with no predicted splice impact. Details ▾Hide ▴

Evidence considered

Variant is missense (Arg to Gly)
not synonymous.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.669. BayesDel score = 0.382927.

8 paper records listed. 2 cited in the classification.

Cited in the classification

Glioma-derived mutations in isocitrate dehydrogenase 2 beneficial to traditional chemotherapy.

IDH2 R172G was generated by site-directed mutagenesis and expressed in rat C6 glioma cells. The mutation diminished wild-type IDH2 enzymatic activity (NADPH production), promoted cell proliferation, and increased sensitivity to chemotherapy agents including adriamycin, cytarabine, teniposide, nimustine, and dactinomycin D.
→ PS3 Names this variant
PMID 21641335 ↗
Source detail

exogenous expression of IDH2R172G reduces the generation of NADPH, which denotes that IDH2R172G mutation diminishes IDH2 activity

Location Results sections 3.2-3.5; Figures 3B, 3C, 4F-J

Context Rat C6 glioma cell line, site-directed mutagenesis, pEGFP-N1-IDH2R172G plasmid, MTT proliferation assay, NADPH enzymatic spectrophotometric assay, chemotherapy sensitivity assay
Glioma derived isocitrate dehydrogenase-2 mutations induced up-regulation of HIF-1α and β-catenin signaling: possible impact on glioma cell metastasis and chemo-resistance.

Fu Y et al. · 2012 May

IDH2 R172G overexpression in C6 glioma cells induced nuclear accumulation of β-catenin, up-regulation of HIF-1α signaling, and increased expression of proteins associated with tumor invasion (N-cadherin, MMP-2, MMP-9) and chemo-resistance.
→ PS3 Names this variant
PMID 22309944 ↗
Source detail

C6 glioma cells transiently over-expressing IDH2R172G induced nuclear accumulation of β-catenin, up-regulation of HIF-1α signaling and corresponding proteins expression that were closely related with tumor invasion and chemo-resistance.

Location Results sections 3.1-3.4; Figures 1-6

Context Rat C6 glioma cell line, pEGFP-N1-IDH2R172G transient overexpression, western blot, gelatin zymography, Matrigel invasion assays

Other recorded publications

The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate.

Characterized the neomorphic enzyme activity of IDH2 R172K in acute myeloid leukemia, demonstrating NADPH-dependent reduction of α-ketoglutarate to 2-hydroxyglutarate. NM_002168.3:c.514A>G (p.Arg172Gly) was not studied or mentioned; experiments focused exclusively on the R172K substitution.
Does not name this variant
PMID 20171147 ↗
Quoted passage
Both IDH1 R132 and IDH2 R172 mutants lack the wild-type enzyme's ability to convert isocitrate to α-ketoglutarate
Results; all functional experiments used IDH2 R172K.
2-hydroxyglutarate production, but not dominant negative function, is conferred by glioma-derived NADP-dependent isocitrate dehydrogenase mutations.

Jin G et al. · 2011

R172G listed among the three IDH2 substitutions observed in gliomas (R172K, R172M, R172G). Functional experiments studied IDH2 R172K only, demonstrating that IDH2 R172 mutants produce 2-hydroxyglutarate but do not exert dominant-negative inhibition of wild-type IDH2. R172G was named but not directly tested in any assay.
Names this variant
PMID 21326614 ↗
Quoted passage
R172K, R172M, and R172G are the IDH2 substitions observed in gliomas.
Introduction (sole mention of R172G); all experimental figures used IDH2 R172K
Modified Rules for Classification of Variants Associated With Disorders of Somatic Mosaicism.

Leon-Quintero FZ et al. · 2025

Describes modified ACMG/AMP rules for variant classification in disorders of somatic mosaicism (DoSMs). The paper proposes adapted criteria for postzygotic variant interpretation. NM_002168.3:c.514A>G (p.Arg172Gly) is not discussed, and IDH2 is not mentioned.
Does not name this variant
PMID 39434542 ↗
Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology.

Schrijver I et al. · 2012

AMP report on opportunities and challenges associated with clinical diagnostic genome sequencing. Discusses NGS technologies, applications in inherited conditions and cancer, and professional implications. IDH2 and R172G are not mentioned in the full text.
Does not name this variant
PMID 22918138 ↗
Chromosomal microarray analysis, including constitutional and neoplastic disease applications, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG).

Shao L et al. · 2021

ACMG technical standard for chromosomal microarray analysis (CMA) in constitutional and neoplastic disease applications, 2021 revision. Describes CMA validation, verification, and clinical applications for copy-number variant detection. IDH2 and R172G are not mentioned in the full text.
Does not name this variant
PMID 34131312 ↗
American College of Medical Genetics and Genomics technical standards and guidelines: microarray analysis for chromosome abnormalities in neoplastic disorders.

Cooley LD et al. · 2013

ACMG technical standards and guidelines for microarray analysis in neoplastic disorders (2013). Describes CMA methodology for chromosome abnormality detection in cancer. IDH2 and R172G are not discussed.
Does not name this variant
PMID 23619274 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 Captured gnomAD v4.1 source record Open source ↗

gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗

SpliceAI Lookup Recorded maximum delta 0.030 Open source ↗

ClinVar 1 Likely pathogenic Open source ↗

COSMIC Captured COSMIC source record Open source ↗

Cancer hotspots Captured Cancer Hotspots source record Open source ↗

OncoKB Captured OncoKB source record Open source ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Likely pathogenic (1 clinical laboratory). (ClinVarID = 376439)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.669. BayesDel score = 0.382927.

Functional

OncoKB identified variant-specific curated literature and context relevant to functional review; curated oncogenicity label: Likely Oncogenic.

Somatic

This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV57468989, n = 48 times).

Cancer Hotspots

This variant lies in a statistically significant hotspot.