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Gene | FGFR2 |
Variant | C382R |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | FGFR2 C382R (also referred to as C383R) lies within the helical domain of the Fgfr2 protein (UniProt.org). C382R results in proliferation similar to wild-type Fgfr2 in a competition assay (PMID: 34272467), but confers a gain of function on the Fgfr2 protein, as demonstrated by constitutive MAPK pathway activation (PMID: 24993163), and transformation of cells in culture (PMID: 24993163, PMID: 34272467). |
Associated Drug Resistance | |
Category Variants Paths |
FGFR2 mutant FGFR2 act mut FGFR2 C382R |
Transcript | NM_000141.5 |
gDNA | chr10:g.121515260A>G |
cDNA | c.1144T>C |
Protein | p.C382R |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_000141 | chr10:g.121515260A>G | c.1144T>C | p.C382R | RefSeq | GRCh38/hg38 |
NM_001320658 | chr10:g.121515260A>G | c.1144T>C | p.C382R | RefSeq | GRCh38/hg38 |
NM_000141.4 | chr10:g.121515260A>G | c.1144T>C | p.C382R | RefSeq | GRCh38/hg38 |
NM_000141.5 | chr10:g.121515260A>G | c.1144T>C | p.C382R | RefSeq | GRCh38/hg38 |
NM_001320658.1 | chr10:g.121515260A>G | c.1144T>C | p.C382R | RefSeq | GRCh38/hg38 |
NM_001320658.2 | chr10:g.121515260A>G | c.1144T>C | p.C382R | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR2 C382R FGFR2 N549D FGFR2 N549H FGFR2 N549K FGFR2 V564L | cholangiocarcinoma | predicted - resistant | Pemigatinib | Case Reports/Case Series | Actionable | In a Phase II trial (FIGHT-207), FGFR2 N549K, FGFR2 V564L, FGFR2 N549D, and FGFR2 N549H were identified in the post-progression circulating tumor DNA of a patient with cholangiocarcinoma harboring FGFR2 C382R who previously responded to Pemazyre (pemigatinib) treatment (PMID: 38710951; NCT03822117). | 38710951 |
FGFR2 C382R FGFR2 N549D | intrahepatic cholangiocarcinoma | predicted - resistant | Erdafitinib | Case Reports/Case Series | Actionable | In a clinical case study, FGFR2 N550D (reported as N549D) was identified in the post-progression tissue biopsy of a patient with intrahepatic cholangiocarcinoma harboring FGFR2 C382R (reported as C383R) who previously responded to treatment with Balversa (erdafitinib) (PMID: 39226398). | 39226398 |
FGFR2 C382R FGFR2 N549D | intrahepatic cholangiocarcinoma | conflicting | Futibatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with intrahepatic cholangiocarcinoma harboring FGFR2 C382R (reported as C383R) and FGFR2 N549D (reported as N550D) experienced progressive disease on treatment with Lytgobi (futibatinib), however, treatment in the patient-derived xenograft (PDX) model resulted in tumor growth inhibition (PMID: 39226398). | 39226398 |
FGFR2 C382R FGFR2 M538I FGFR2 N550D FGFR2 V565I | intrahepatic cholangiocarcinoma | predicted - sensitive | Tinengotinib | Case Reports/Case Series | Actionable | In a clinical case study, Tinengotinib (TT-00420) treatment resulted in 37% tumor shrinkage in a patient with intrahepatic cholangiocarcinoma harboring FGFR2 C382R, N550D, V565I, and M538I (PMID: 39706336). | 39706336 |