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Gene | FGFR2 |
Variant | E566A |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | FGFR2 E566A (corresponds to E565A in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E566A results in increased Fgfr2 autophosphorylation and substrate phosphorylation in in vitro kinase assays (PMID: 17803937, PMID: 28166054) and is also associated with resistance to FGFR inhibitors (PMID: 31109923). |
Associated Drug Resistance | Y |
Transcript | NM_022970 |
gDNA | chr10:g.121496701T>G |
cDNA | c.1697A>C |
Protein | p.E566A |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_022970 | chr10:g.121496701T>G | c.1697A>C | p.E566A | RefSeq | GRCh38/hg38 |
NM_022970.3 | chr10:g.121496701T>G | c.1697A>C | p.E566A | RefSeq | GRCh38/hg38 |
XM_024447887.1 | chr10:g.121488070T>G | c.1697A>C | p.E566A | RefSeq | GRCh38/hg38 |
NM_001144913 | chr10:g.121496701T>G | c.1697A>C | p.E566A | RefSeq | GRCh38/hg38 |
NM_001144913.1 | chr10:g.121496701T>G | c.1697A>C | p.E566A | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR2 - ZMYM4 FGFR2 N550H FGFR2 N550K FGFR2 V565F FGFR2 E566A FGFR2 K660M | intrahepatic cholangiocarcinoma | resistant | Infigratinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with intrahepatic cholangiocarcinoma harboring an FGFR2-ZMYM4 fusion developed progressive disease after initial response to Infigratinib (BGJ398) for 5.6 months and FGFR2 V565F, K660M E566A, N550H, and N550K mutations were identified in the post-progression cell-free DNA (PMID: 31109923). | 31109923 |
FGFR2 - ZMYM4 FGFR2 N550H FGFR2 N550K FGFR2 V565F FGFR2 E566A FGFR2 K660M | intrahepatic cholangiocarcinoma | sensitive | Futibatinib | Case Reports/Case Series | Actionable | In a Phase I trial, a patient with intrahepatic cholangiocarcinoma, harboring an FGFR2-ZMYM4 fusion with FGFR2 V565F, K660M E566A, N550H, and N550K mutations, responded to TAS-120 for 7.2 months before progressing due to an acquired FGFR2 V563L mutation, detected in cell-free DNA (PMID: 31109923; NCT02052778). | 31109923 |
FGFR2 - INA FGFR2 V565L FGFR2 E566A | intrahepatic cholangiocarcinoma | resistant | Futibatinib | Case Reports/Case Series | Actionable | In a Phase I trial, a patient with intrahepatic cholangiocarcinoma, harboring an FGFR2-INA fusion with FGFR2 H683L, L618V, N550H, N550T, M538I mutations, responded to TAS-120 for 5.1 months before progressing due to acquired FGFR2 V565L and E566A mutations, detected in cell-free DNA (PMID: 31109923; NCT02052778). | 31109923 |
FGFR2 fusion FGFR2 E566A | intrahepatic cholangiocarcinoma | decreased response | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Infigratinib (BGJ398) treatment of intrahepatic cholangiocarcinoma cells with an FGFR2 fusion in context with FGFR2 E566A had weakened sensitivity, as demonstrated by cell viability and downstream signaling assays (PMID: 31109923). | 31109923 |
FGFR2 fusion FGFR2 E566A | intrahepatic cholangiocarcinoma | decreased response | Debio 1347 | Preclinical - Cell culture | Actionable | In a preclinical study, Debio 1347 treatment of intrahepatic cholangiocarcinoma cells with an FGFR2 fusion in context with FGFR2 E566A had weakened sensitivity, as demonstrated by cell viability and downstream signaling assays (PMID: 31109923). | 31109923 |
FGFR2 fusion FGFR2 E566A | intrahepatic cholangiocarcinoma | sensitive | Futibatinib | Preclinical - Cell culture | Actionable | In a preclinical study, TAS-120 treatment of intrahepatic cholangiocarcinoma cells with an FGFR2 fusion in context with FGFR2 E566A were sensitive to treatment as demonstrated by decreased cell viability and decreased activation of downstream signaling (PMID: 31109923). | 31109923 |
Molecular Profile | Protein Effect | Treatment Approaches |
---|---|---|
FGFR2 E566A | gain of function | FGFR Inhibitor (Pan) FGFR2 Inhibitor |
FGFR2 - ZMYM4 FGFR2 N550H FGFR2 N550K FGFR2 V565F FGFR2 E566A FGFR2 K660M | ||
FGFR2 - INA FGFR2 V565L FGFR2 E566A | ||
FGFR2 fusion FGFR2 E566A |