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Gene | IDH2 |
Variant | R172S |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | IDH2 R172S lies within the active site of the Idh2 protein (PMID: 19228619). R172S confers a gain of function to the Idh2 protein as demonstrated by accumulation 2HG (R(-)-2-hydroxyglutarate), and leads to increased migration in cultured cells (PMID: 23264629, PMID: 27913435). |
Associated Drug Resistance | |
Category Variants Paths |
IDH2 mutant IDH2 act mut IDH2 R172S IDH2 mutant IDH2 R172X IDH2 R172S |
Transcript | NM_002168.4 |
gDNA | chr15:g.90088605C>G |
cDNA | c.516G>C |
Protein | p.R172S |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_002168 | chr15:g.90088605C>G | c.516G>C | p.R172S | RefSeq | GRCh38/hg38 |
NM_002168.3 | chr15:g.90088605C>G | c.516G>C | p.R172S | RefSeq | GRCh38/hg38 |
NM_002168.4 | chr15:g.90088605C>G | c.516G>C | p.R172S | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
IDH2 R172S | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172S is on the companion diagnostic. | 28588020 detail... detail... |
IDH2 R172S | chondrosarcoma | sensitive | Ceralasertib + Olaparib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Lynparza (olaparib) and Ceralasertib (AZD6738) resulted in a greater decrease in cell viability compared to Ceralasertib (AZD6738) alone in chondrosarcoma cells harboring IDH2 R172S in culture (PMID: 34027408). | 34027408 |