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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

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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

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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 Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 act mut Advanced Solid Tumor decreased response Cediranib Preclinical Actionable In a preclinical study, transformed cells expressing constitutively active FGFR2 demonstrated reduced sensitivity to inhibition of receptor phosphorylation and cell proliferation by Cediranib (AZD-2171) in culture, when compared to other tyrosine kinase inhibitors (PMID: 22238366). 22238366
FGFR2 act mut Advanced Solid Tumor decreased response Nintedanib Preclinical Actionable In a preclinical study, transformed cells expressing constitutively active FGFR2 demonstrated reduced sensitivity to Ofev (Nintedanib) in culture, when compared to other tyrosine kinase inhibitors (PMID: 22238366). 22238366
FGFR2 act mut Advanced Solid Tumor decreased response Brivanib Preclinical Actionable In a preclinical study, transformed cells expressing constitutively active FGFR2 demonstrated reduced sensitivity to inhibition of receptor phosphorylation and cell proliferation by Brivanib (BMS-540215) in culture, when compared to other tyrosine kinase inhibitors (PMID: 22238366). 22238366
FGFR2 act mut stomach carcinoma sensitive S-49076 Preclinical - Cell line xenograft Actionable In a preclinical study, S-49076 inhibited Met activation, resulting in growth inhibition of gastric carcinoma cells harboring FGFR2 activating mutations in culture and in cell line xenograft models (PMID: 23804704). 23804704
FGFR2 act mut Advanced Solid Tumor predicted - sensitive Erdafitinib Phase I Actionable In a Phase I trial, Balversa (erdafitinib) treatment resulted in stable disease in 70% (16/23) and partial response in 22% (5/23) of patients with advanced solid tumors harboring FGFR 1-4 activating mutations (including amplifications, mutations and translocations), while no antitumor activity was observed in patients with unknown or no known changes in FGFR (PMID: 26324363; NCT01703481). 26324363
FGFR2 act mut Advanced Solid Tumor predicted - sensitive AZD4547 Phase II 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%, with a partial response in 1 and stable disease in 2 of 12 patients with FGFR2 activating mutations (PMID: 32463741; NCT02465060). 32463741
FGFR2 act mut Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited receptor phosphorylation and cell growth in transformed cells expressing constitutively active FGFR2 in culture (PMID: 22238366). 22238366
FGFR2 act mut Advanced Solid Tumor sensitive Debio 1347 Phase I Actionable In a Phase I trial, Debio 1347 (CH5183284) dosing regimen has been determined in solid tumor patients with activating FGFR2 alterations (JCO, Vol 33, No 15_suppl (May 20 Supplement), 2015: 2540). detail...
FGFR2 act mut endometrial cancer sensitive Dovitinib Preclinical - Cell line xenograft Actionable In a preclinical study, both cell lines and cell line xenograft models of endometrial cancer with FGFR2 activating mutations showed greater sensitivity to Dovitinib (TKI258) as compared to FGFR2 wild-type (PMID: 23443805). 23443805
FGFR2 act mut Advanced Solid Tumor sensitive Dovitinib Preclinical Actionable In a preclinical study, Dovitinib (TKI258) inhibited receptor phosphorylation and cell proliferation in transformed cells expressing constitutively active FGFR2 in culture (PMID: 22238366). 22238366
FGFR2 mutant transitional cell carcinoma sensitive Erdafitinib Guideline Actionable Balversa (erdafitinib) is included in the guidelines for patients with advanced or metastatic urothelial carcinoma harboring Fgfr2 alterations after progression on platinum-based regimens (NCCN.org). detail...
FGFR2 mutant transitional cell carcinoma sensitive Erdafitinib FDA approved - Has Companion Diagnostic Actionable In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations (PMID: 31340094; NCT02365597). detail... 31340094 detail...
FGFR2 mutant endometrial cancer sensitive Infigratinib Preclinical Actionable In a preclinical study, Infigratinib (BGJ398) inhibited the growth of FGFR2-mutated endometrial cancer cells in vitro and in xenograft models (PMID: 23443805). 23443805
FGFR2 mutant endometrial cancer sensitive PRN1371 Preclinical - Cell culture Actionable In a preclinical study, PRN1371 inhibited proliferation of endometrial cancer cells harboring FGFR2 mutations in culture (AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1249). detail...
FGFR2 mutant cholangiocarcinoma sensitive Infigratinib Case Reports/Case Series Actionable In a Phase I trial, a patient with cholangiocarcinoma harboring an FGFR2 mutation demonstrated a decreased tumor burden when treated with Infigratinib (BGJ398) (PMID: 27870574). 27870574
FGFR2 mutant bladder urothelial carcinoma sensitive Erdafitinib FDA approved - Has Companion Diagnostic Actionable In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations (PMID: 31340094; NCT02365597). detail... 31340094 detail...
FGFR2 mutant bladder urothelial carcinoma sensitive Erdafitinib Guideline Actionable Balversa (erdafitinib) is included in the guidelines for patients with advanced or metastatic urothelial carcinoma harboring Fgfr2 alterations after progression on platinum-based regimens (NCCN.org). detail...
FGFR2 mutant cholangiocarcinoma predicted - sensitive Erdafitinib Phase I Actionable In a Phase I trial, Balversa (erdafitinib) treatment resulted in an objective response rate of 27% (3/11) in patients with cholangiocarcinoma harboring FGFR genomic alterations, including 1 with FGFR2 mutation, 2 with FGFR3 mutations, and 8 with FGFR2 fusions (PMID: 31088831; NCT01703481). 31088831
FGFR2 mutant Advanced Solid Tumor predicted - sensitive Debio 1347 Phase I Actionable In a Phase I trial, Debio 1347 treatment resulted in partial response in 10.5% (6/57) and stable disease in 28.1% (16/57) of patients with advanced solid tumors harboring genomic alterations of FGFR1/2/3, including amplifications, fusions, and mutations (PMID: 30745300; NCT01948297). 30745300
FGFR2 mutant Advanced Solid Tumor sensitive Pemigatinib Preclinical - Cell culture Actionable In a preclinical study, a variety of cancer cell lines harboring mutations in FGFR1, FGFR2, and/or FGFR3 demonstrated sensitivity to Pemazyre (pemigatinib) in culture and in cell line xenograft models, resulting in inhibition of tumor growth (Cancer Res 2015;75(15 Suppl):Abstract nr 771). detail...