Gene Variant Detail

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Gene FGFR2
Variant E565A
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions FGFR2 E565A lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E565A demonstrates resistance to FGFR inhibitors in the context of FGFR2-SHTN1 in culture (PMID: 31911531), and results in increased Fgfr2 autophosphorylation and substrate phosphorylation in in vitro kinase assays (PMID: 17803937, PMID: 28166054).
Associated Drug Resistance Y

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Transcript NM_000141
gDNA chr10:g.121496701T>G
cDNA c.1694A>C
Protein p.E565A
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_000141 chr10:g.121496701T>G c.1694A>C p.E565A RefSeq GRCh38/hg38
XM_017015922 chr10:g.121488070T>G c.1694A>C p.E565A RefSeq GRCh38/hg38

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  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 - ZMYM4 FGFR2 N549H FGFR2 N549K FGFR2 V564F FGFR2 E565A FGFR2 K659M cholangiocarcinoma predicted - resistant Infigratinib Case Reports/Case Series Actionable In a clinical case study, FGFR2 mutations E565A, K659M, N549H, N549K and V564F were identified in the cell-free DNA of a cholangiocarcinoma patient harboring FGFR2-ZMYM4 fusion after the patient progressed while on Infigratinib (BGJ398) treatment (PMID: 28034880). 28034880
FGFR2 - OPTN FGFR2 N549H FGFR2 V564F FGFR2 E565A FGFR2 L617V FGFR2 K641R cholangiocarcinoma predicted - resistant Infigratinib Case Reports/Case Series Actionable In a clinical case study, FGFR2 mutations E565A, K641R, L617V, N549H and V564F were identified in the cell-free DNA of a cholangiocarcinoma patient harboring FGFR2-OPTN fusion after the patient progressed while on Infigratinib (BGJ398) treatment (PMID: 28034880). 28034880
FGFR2 - SHTN1 FGFR2 E565A cholangiocarcinoma resistant AZD4547 Preclinical - Cell culture Actionable In a preclinical study, cholangiocarcinoma cells expressing both FGFR2-SHTN1 and FGFR2 E565A demonstrated resistance to treatment with AZD4547 in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 E565A Advanced Solid Tumor sensitive Ponatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing both FGFR2-SHTN1 and FGFR2 E565A were sensitive to treatment with Iclusig (ponatinib) in culture, demonstrating reduced cell viability (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 E565A Advanced Solid Tumor resistant Infigratinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing both FGFR2-SHTN1 and FGFR2 E565A demonstrated resistance to treatment with Infigratinib (BGJ398) in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 E565A Advanced Solid Tumor sensitive Ponatinib + Sapanisertib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Iclusig (ponatinib) and Sapanisertib (MLN0128) resulted in synergistic effects in transformed cells expressing both FGFR2-SHTN1 and FGFR2 E565A in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 E565A cholangiocarcinoma resistant Infigratinib Preclinical - Cell culture Actionable In a preclinical study, cholangiocarcinoma cells expressing both FGFR2-SHTN1 and FGFR2 E565A demonstrated resistance to treatment with Infigratinib (BGJ398) in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 E565A cholangiocarcinoma resistant Futibatinib Preclinical - Cell culture Actionable In a preclinical study, cholangiocarcinoma cells expressing both FGFR2-SHTN1 and FGFR2 E565A demonstrated resistance to treatment with Futibatinib (TAS-120) in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 E565A Advanced Solid Tumor sensitive Erdafitinib + Sapanisertib Preclinical - Cell culture Actionable In a preclinical study, the addition of Sapanisertib (MLN0128) therapy restored the sensitivity of transformed cells expressing both FGFR2-SHTN1 and FGFR2 E565A to treatment with Balversa (erdafitinib), demonstrating synergistic effects (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 E565A Advanced Solid Tumor sensitive AZD4547 + Sapanisertib Preclinical - Cell culture Actionable In a preclinical study, the addition of Sapanisertib (MLN0128) therapy restored the sensitivity of transformed cells expressing both FGFR2-SHTN1 and FGFR2 E565A to treatment with AZD4547, demonstrating synergistic effects (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 E565A Advanced Solid Tumor resistant AZD4547 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing both FGFR2-SHTN1 and FGFR2 E565A demonstrated resistance to treatment with AZD4547 in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 E565A Advanced Solid Tumor resistant Dovitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing both FGFR2-SHTN1 and FGFR2 E565A demonstrated resistance to treatment with Dovitinib (TKI258) in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 E565A Advanced Solid Tumor resistant Futibatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing both FGFR2-SHTN1 and FGFR2 E565A demonstrated resistance to treatment with Futibatinib (TAS-120) in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 E565A Advanced Solid Tumor resistant Erdafitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing both FGFR2-SHTN1 and FGFR2 E565A demonstrated resistance to treatment with Balversa (erdafitinib) in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 E565A cholangiocarcinoma sensitive Ponatinib Preclinical - Cell culture Actionable In a preclinical study, cholangiocarcinoma cells expressing both FGFR2-SHTN1 and FGFR2 E565A were sensitive to treatment with Iclusig (ponatinib) in culture, demonstrating reduced cell viability (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 E565A cholangiocarcinoma resistant Erdafitinib Preclinical - Cell culture Actionable In a preclinical study, cholangiocarcinoma cells expressing both FGFR2-SHTN1 and FGFR2 E565A demonstrated resistance to treatment with Balversa (erdafitinib) in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 E565A cholangiocarcinoma resistant Dovitinib Preclinical - Cell culture Actionable In a preclinical study, cholangiocarcinoma cells expressing both FGFR2-SHTN1 and FGFR2 E565A demonstrated resistance to treatment with Dovitinib (TKI258) in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 E565A FGFR2 L617M Advanced Solid Tumor sensitive Infigratinib + Sapanisertib Preclinical - Cell culture Actionable In a preclinical study, the addition of Sapanisertib (MLN0128) therapy restored the sensitivity of transformed cells expressing both FGFR2-SHTN1 and FGFR2 E565A to treatment with Infigratinib (BGJ398), demonstrating synergistic effects (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 E565A FGFR2 L617M cholangiocarcinoma predicted - resistant Infigratinib Case Reports/Case Series Actionable In a Phase II trial, a patient with cholangiocarcinoma harboring FGFR2-SHTN1 initially responded to treatment with Infigratinib (BGJ398), but progressed after eight months and via repeat tissue biopsy was found to have acquired FGFR2 E565A, and via circulating tumor DNA testing, FGFR2 L617M (PMID: 31911531). 31911531
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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...
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