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Gene | FGFR2 |
Variant | Y376C |
Impact List | missense |
Protein Effect | gain of function - predicted |
Gene Variant Descriptions | FGFR2 Y376C (corresponds to Y375C in the canonical isoform) lies within the extracellular domain of the Fgfr2 protein (PMID: 17525745). Y376C results in constitutive dimerization through inter-molecular disulfide bonds (PMID: 17525745), and therefore, is predicted to lead to a gain of Fgfr2 protein function. |
Associated Drug Resistance | |
Category Variants Paths |
FGFR2 mutant FGFR2 act mut FGFR2 Y376C |
Transcript | NM_022970.4 |
gDNA | chr10:g.121515280T>C |
cDNA | c.1127A>G |
Protein | p.Y376C |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001144913.1 | chr10:g.121515280T>C | c.1127A>G | p.Y376C | RefSeq | GRCh38/hg38 |
NM_001144913.1 | chr10:g.121515280T>C | c.1127A>G | p.Y376C | RefSeq | GRCh38/hg38 |
NM_001144913 | chr10:g.121515280T>C | c.1127A>G | p.Y376C | RefSeq | GRCh38/hg38 |
NM_022970.3 | chr10:g.121515280T>C | c.1127A>G | p.Y376C | RefSeq | GRCh38/hg38 |
NM_022970 | chr10:g.121515280T>C | c.1127A>G | p.Y376C | RefSeq | GRCh38/hg38 |
NM_022970.4 | chr10:g.121515280T>C | c.1127A>G | p.Y376C | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR2 Y376C | intrahepatic cholangiocarcinoma | predicted - sensitive | Fexagratinib | Case Reports/Case Series | Actionable | In a Phase II (MATCH) trial, AZD4547 treatment resulted in an overall response rate of 10.5% (2/19) in patients with advanced solid tumors harboring FGFR2 or 3 activating single nucleotide variants and a 6-month progression-free survival rate of 6%, including a partial response with 69% reduction in target lesion size and progression-free survival of 9.8 months in a patient with intrahepatic cholangiocarcinoma harboring FGFR2 Y376C (PMID: 32463741; NCT02465060). | 32463741 |