FGFR2 W290_I291delinsC: Gene Variant Detail - Cancer Knowledgebase (CKB)

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Gene	FGFR2
Variant	W290_I291delinsC
Impact List	indel
Protein Effect	gain of function
Gene Variant Descriptions	FGFR2 W290_I291delinsC results in a deletion of tryptophan (W) at amino acid 290 and isoleucine (I) at amino acid 291 within the Ig3 region of Fgfr2, combined with the insertion of a cysteine (C) at the same site (UniProt.org). W290_I291delinsC confers a gain of function on Fgfr2, as demonstrated by ligand-independent phosphorylation, dimerization, and oncogenic transformation (PMID: 26048680).
Associated Drug Resistance
Category Variants Paths	FGFR2 mutant FGFR2 act mut FGFR2 W290_I291delinsC FGFR2 mutant FGFR2 exon7 FGFR2 exon 7 del FGFR2 W290_I291delinsC

Variant Reference Transcript
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Transcript	NM_000141.5
gDNA	chr10:g.121520046_121520048delATC
cDNA	c.870_872delGAT
Protein	p.W290_I291delinsC
Source Database	RefSeq
Genome Build	GRCh38/hg38

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Showing 1 to 15 of 15 entries

Transcript	gDNA	cDNA	Protein	Source Database	Genome Build
NM_000141	chr10:g.121520046_121520048delATC	c.870_872delGAT	p.W290_I291delinsC	RefSeq	GRCh38/hg38
NM_000141.4	chr10:g.121520046_121520048delATC	c.870_872delGAT	p.W290_I291delinsC	RefSeq	GRCh38/hg38
NM_000141.5	chr10:g.121520046_121520048delATC	c.870_872delGAT	p.W290_I291delinsC	RefSeq	GRCh38/hg38
NM_001144913	chr10:g.121520046_121520048delATC	c.870_872delGAT	p.W290_I291delinsC	RefSeq	GRCh38/hg38
NM_001144913.1	chr10:g.121520046_121520048delATC	c.870_872delGAT	p.W290_I291delinsC	RefSeq	GRCh38/hg38
NM_001144913.1	chr10:g.121520046_121520048delATC	c.870_872delGAT	p.W290_I291delinsC	RefSeq	GRCh38/hg38
NM_001144917	chr10:g.121520046_121520048delATC	c.870_872delGAT	p.W290_I291delinsC	RefSeq	GRCh38/hg38
NM_001144917.1	chr10:g.121520046_121520048delATC	c.870_872delGAT	p.W290_I291delinsC	RefSeq	GRCh38/hg38
NM_001144917.2	chr10:g.121520046_121520048delATC	c.870_872delGAT	p.W290_I291delinsC	RefSeq	GRCh38/hg38
NM_001320658	chr10:g.121520046_121520048delATC	c.870_872delGAT	p.W290_I291delinsC	RefSeq	GRCh38/hg38
NM_001320658.1	chr10:g.121520046_121520048delATC	c.870_872delGAT	p.W290_I291delinsC	RefSeq	GRCh38/hg38
NM_001320658.2	chr10:g.121520046_121520048delATC	c.870_872delGAT	p.W290_I291delinsC	RefSeq	GRCh38/hg38
NM_022970	chr10:g.121520046_121520048delATC	c.870_872delGAT	p.W290_I291delinsC	RefSeq	GRCh38/hg38
NM_022970.3	chr10:g.121520046_121520048delATC	c.870_872delGAT	p.W290_I291delinsC	RefSeq	GRCh38/hg38
NM_022970.4	chr10:g.121520046_121520048delATC	c.870_872delGAT	p.W290_I291delinsC	RefSeq	GRCh38/hg38

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Showing 1 to 35 of 35 entries

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
FGFR2 act mut	ethmoid sinus cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with ethmoid sinus cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
FGFR2 act mut	supraglottis cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with supraglottic larynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
FGFR2 act mut	hypopharynx cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with hypopharynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
FGFR2 act mut	breast cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with stage IV (M1) breast cancer harboring FGFR fusion or mutations (NCCN.org).	detail...
FGFR2 act mut	maxillary sinus cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with maxillary sinus cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
FGFR2 act mut	glottis cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with glottic larynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
FGFR2 act mut	oral cavity cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with oral cavity cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
FGFR2 act mut	oropharynx cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with oropharynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
FGFR2 act mut	salivary gland cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with unresectable locally advanced, recurrent, or metastatic salivary gland tumors harboring FGFR mutations or fusions (category 2B) who received prior systemic therapy and have no alternative systemic therapy available (NCCN.org).	detail...
FGFR2 act mut	lung non-small cell carcinoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring oncogenic or likely oncogenic FGFR alterations (NCCN.org).	detail...
FGFR2 act mut	Advanced Solid Tumor	predicted - sensitive	Erdafitinib	Phase II	Actionable	In a Phase II trial (RAGNAR), Balversa (erdafitinib) treatment resulted in an objective response rate of 29.5% (64/217, 6 complete and 58 partial responses), a disease control rate of 74%, clinical benefit rate of 46%, a median duration of response of 6.9 months, median progression-free survival of 4.2 months, and median overall survival of 10.7 months in patients with advanced solid tumors harboring FGFR1, FGFR2, or FGFR3 mutations or fusions (PMID: 37541273; NCT04083976).	37541273
FGFR2 act mut	Advanced Solid Tumor	predicted - sensitive	Fexagratinib	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 mutant	intrahepatic cholangiocarcinoma	predicted - sensitive	Derazantinib	Phase II	Actionable	In a Phase II trial (FIDES-01), Derazantinib (ARQ 087) treatment resulted in an objective response rate of 6.5%, a disease control rate of 58.1%, median progression-free survival of 8.3 months, and a median overall survival of 15.9 months in patients with intrahepatic cholangiocarcinoma harboring an FGFR2 mutation or amplification (Ann Oncol (2022) 33 (suppl_7): S19-S26; NCT03230318).	detail...
FGFR2 mutant	transitional cell carcinoma	predicted - sensitive	Cetrelimab + Erdafitinib	Phase II	Actionable	In a Phase II trial, the combination of Balversa (erdafitinib) and Cetrelimab (JNJ-63723283) treatment resulted in an overall response rate of 54.5% (6 complete responses), disease control rate of 79.5%, median duration of response of 11.10 months, median progression-free survival of 10.97 months, and a 12-month overall survival of 68% in patients with metastatic urothelial carcinoma harboring FGFR mutations (J Clin Oncol 41, 2023 (suppl 16; abstr 4504); NCT03473743).	detail...
FGFR2 act mut	transitional cell carcinoma	no benefit	Derazantinib	Phase Ib/II	Actionable	In a Phase I/II trial (FIDES-02), Derazantinib (ARQ 087) treatment was well tolerated but demonstrated limited efficacy in patients with urothelial carcinoma harboring FGFR1 (n=4), FGFR2 (n=7), or FGFR3 (n=35) mutations or FGFR3 fusions (n=6), with an objective response rate of 8.2% (4/49, all partial responses) and disease control rate of 30.6% (15/49) by independent central review (PMID: 38627238; NCT04045613).	38627238
FGFR2 act mut	Advanced Solid Tumor	sensitive	Zoligratinib	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	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	KIN-3248	Phase I	Actionable	In a Phase I trial, KIN-3248 treatment demonstrated safety and preliminary activity in patients with advanced solid tumors harboring alterations in FGFR2 or FGFR3, resulting in an objective response rate of 9.25% (5/54, 5 partial responses) and disease control rate of 46% (25/54), with stable disease in 20 patients (PMID: 38602417; NCT05242822).	38602417
FGFR2 mutant	Advanced Solid Tumor	predicted - sensitive	Zoligratinib	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	predicted - sensitive	ICP-192	Phase I	Actionable	In a Phase I trial, ICP-192 (gunagratinib) was well-tolerated, and resulted in an overall response rate or 33.3% (4/12, 1 complete response, 3 partial response) and a disease control rate of 91.7% (11/12) in patients with advanced solid tumors harboring FGF/FGFR gene aberrations (J Clin Oncol 39, 2021 (suppl 15; abstr 4092); NCT03758664).	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 act mut	cholangiocarcinoma	predicted - sensitive	Tinengotinib	Clinical Study	Actionable	In a combined analysis of 3 clinical trials, Tinengotinib (TT-00420) resulted in an overall response rate (ORR) of 20.7% and disease control rate (DCR) of 75.9% in cholangiocarcinoma patients (n=58), and in patients with FGFR2 mutations (n=29), an ORR of 34% and DCR of 89.7% and ORR of 38.1%, DCR of 95.2%, and median progression-free survival of 6.9 mo in patients with prior FGFR inhibitor resistance (n=21) (Ann Oncol (2023) 34 (suppl_2): S215-S216; NCT03654547, NCT04742959, NCT04919642).	detail...
FGFR2 mutant	breast cancer	no benefit	Sunitinib	Case Reports/Case Series	Actionable	In a Phase II trial (TAPUR), Sutent (sunitinib) treatment did not meet the predetermined efficacy criteria in metastatic breast cancer patients with FGFR2 amplification (n=2), FGFR2 mutation (including FGFR2 rearrangement) (n=6), or both (n=2), resulting in no objective responses or stable disease of at least 16 weeks, median progression-free survival of 8 weeks, and a median overall survival of 22 weeks (PMID: 38354330; NCT02693535).	38354330
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 Truseltiq (infigratinib) (PMID: 27870574).	27870574
FGFR2 mutant	Advanced Solid Tumor	predicted - sensitive	Erdafitinib	Case Reports/Case Series	Actionable	In a Phase II trial (MATCH), Balversa (erdafitinib) treatment resulted in an objective response rate of 16% (4/25), median progression-free survival of 3.6 months, and median overall survival of 11.0 months in patients with advanced solid tumors harboring FGFR1, FGFR2, or FGFR3 mutations or fusions (PMID: 38603650; NCT02465060).	38603650
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	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 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	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 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	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	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	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 mutant	endometrial cancer	sensitive	Infigratinib	Preclinical	Actionable	In a preclinical study, Truseltiq (infigratinib) inhibited the growth of FGFR2-mutated endometrial cancer cells in vitro and in xenograft models (PMID: 23443805).	23443805

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FGFR2 W290_I291delinsC - Gene Variant Detail

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