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Gene | FGFR2 |
Variant | S252W |
Impact List | missense |
Protein Effect | gain of function - predicted |
Gene Variant Descriptions | FGFR2 S252W lies within the extracellular domain of the Fgfr2 protein (UniProt.org). S252W results in a growth advantage relative to wild-type Fgfr2 in a competition assay and transformation activity similar to overexpressed Fgfr2 in cultured cells (PMID: 34272467), and results in loss of ligand specificity, increased Fgfr2 phosphorylation, increased FGF7-stimulated shedding of HB-EGF, and is transforming in cell culture (PMID: 11121055, PMID: 18552176, PMID: 37759450), 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 S252W FGFR2 mutant FGFR2 exon7 FGFR2 S252W |
Transcript | NM_000141.5 |
gDNA | chr10:g.121520163G>C |
cDNA | c.755C>G |
Protein | p.S252W |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_022970 | chr10:g.121520163G>C | c.755C>G | p.S252W | RefSeq | GRCh38/hg38 |
NM_001320658.1 | chr10:g.121520163G>C | c.755C>G | p.S252W | RefSeq | GRCh38/hg38 |
NM_001320658 | chr10:g.121520163G>C | c.755C>G | p.S252W | RefSeq | GRCh38/hg38 |
NM_000141 | chr10:g.121520163G>C | c.755C>G | p.S252W | RefSeq | GRCh38/hg38 |
NM_001144913.1 | chr10:g.121520163G>C | c.755C>G | p.S252W | RefSeq | GRCh38/hg38 |
NM_000141.4 | chr10:g.121520163G>C | c.755C>G | p.S252W | RefSeq | GRCh38/hg38 |
NM_001144917.2 | chr10:g.121520163G>C | c.755C>G | p.S252W | RefSeq | GRCh38/hg38 |
NM_001144913.1 | chr10:g.121520163G>C | c.755C>G | p.S252W | RefSeq | GRCh38/hg38 |
NM_022970.4 | chr10:g.121520163G>C | c.755C>G | p.S252W | RefSeq | GRCh38/hg38 |
NM_001144917 | chr10:g.121520163G>C | c.755C>G | p.S252W | RefSeq | GRCh38/hg38 |
NM_001144917.1 | chr10:g.121520163G>C | c.755C>G | p.S252W | RefSeq | GRCh38/hg38 |
NM_022970.3 | chr10:g.121520163G>C | c.755C>G | p.S252W | RefSeq | GRCh38/hg38 |
NM_001320658.2 | chr10:g.121520163G>C | c.755C>G | p.S252W | RefSeq | GRCh38/hg38 |
NM_001144913 | chr10:g.121520163G>C | c.755C>G | p.S252W | RefSeq | GRCh38/hg38 |
NM_000141.5 | chr10:g.121520163G>C | c.755C>G | p.S252W | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR2 S252W | endometrial cancer | decreased response | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, endometrial cells harboring Fgfr2 S252W were less sensitive to the anti-proliferative effects of AZD4547 than the Fgfr2 double mutant, K310R, N550K (PMID: 26294741). | 26294741 |
FGFR2 S252W | Advanced Solid Tumor | predicted - sensitive | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 S252W were sensitive to treatment with AZD4547 in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 S252W | Advanced Solid Tumor | predicted - sensitive | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 S252W were sensitive to treatment with Truseltiq (infigratinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 S252W | endometrial cancer | decreased response | Dovitinib | Preclinical | Actionable | In a preclinical study, Dovitinib (TKI258) did not potently inhibit cell proliferation in endometrial cancer cells harboring FGFR2 S252W mutation in culture (PMID: 22238366). | 22238366 |
FGFR2 S252W | Advanced Solid Tumor | conflicting | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 S252W were resistant to treatment with Dovitinib (TKI258) in culture (PMID: 34272467). | 34272467 |
FGFR2 S252W | Advanced Solid Tumor | conflicting | Dovitinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FGFR2 S252W were sensitive to Dovitinib (TKI258) (PMID: 23908597). | 23908597 |
FGFR2 S252W | endometrial cancer | sensitive | Nintedanib | Preclinical | Actionable | In a preclinical study, Ofev (Nintedanib) inhibited cell proliferation in endometrial cancer cells harboring FGFR2 S252W mutation in culture (PMID: 22238366). | 22238366 |
FGFR2 S252W | gallbladder adenocarcinoma | predicted - sensitive | Pazopanib | Case Reports/Case Series | Actionable | In a clinical case study, Votrient (pazopanib) treatment resulted in stable disease lasting over 2 years in a patient with metastatic gallbladder adenocarcinoma harboring FGFR2 S252W (PMID: 36307559). | 36307559 |
FGFR2 S252W | endometrial cancer | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, Iclusig (ponatinib) inhibited Fgfr2 phosphorylation and cell proliferation in endometrial cancer cells harboring FGFR2 S252W in culture (PMID: 22238366). | 22238366 |
FGFR2 S252W | endometrial carcinoma | decreased response | RO4987655 | Preclinical - Cell culture | Actionable | In a preclinical study, endometrial carcinoma cells harboring FGFR2 S252W demonstrated decreased response to RO4987655 in culture (PMID: 26438159). | 26438159 |
FGFR2 S252W | endometrial carcinoma | decreased response | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, endometrial carcinoma cells harboring FGFR2 S252W demonstrated decreased sensitivity to Selumetinib (AZD-6244) in culture (PMID: 26438159). | 26438159 |
FGFR2 S252W | endometrial cancer | sensitive | Brivanib | Preclinical | Actionable | In a preclinical study, Brivanib (BMS-540215) inhibited growth of endometrial cancer cells harboring FGFR2 S252W in culture (PMID: 22238366). | 22238366 |
FGFR2 S252W | endometrial cancer | sensitive | Cediranib | Preclinical | Actionable | In a preclinical study, Cediranib (AZD-2171) inhibited growth of endometrial cancer cells harboring FGFR2 S252W in culture (PMID: 22238366). | 22238366 |
FGFR2 S252W | endometrial cancer | sensitive | Zoligratinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Debio 1347 inhibited proliferation of endometrial cancer cells harboring an FGFR2 S252W mutation in culture and inhibited tumor growth in FGFR2 S252W-positive endometrial cancer cell line xenograft models (PMID: 25169980). | 25169980 |
FGFR2 S252W | adenoid cystic carcinoma | 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 FGFR1-3 mutations or fusions, including a partial response in a patient with adenoid cystic carcinoma of the submandibular gland harboring FGFR2 S252W (PMID: 38603650; NCT02465060). | 38603650 |
FGFR2 S252W | Advanced Solid Tumor | predicted - sensitive | Erdafitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 S252W were sensitive to treatment with Balversa (erdafitinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 S252W | endometrial cancer | predicted - sensitive | Futibatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lytgobi (futibatinib) treatment led to inhibition of cell proliferation in an endometrial cancer cell line harboring FGFR2 S252W in culture (PMID: 32973082). | 32973082 |
FGFR2 S252W | Advanced Solid Tumor | predicted - sensitive | Futibatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 S252W were sensitive to treatment with Lytgobi (futibatinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 S252W | endometrial carcinoma | sensitive | RO5126766 | Preclinical - Cell culture | Actionable | In a preclinical study, RO5126766 inhibited proliferation of endometrial carcinoma cells harboring FGFR2 S252W in culture (PMID: 26438159). | 26438159 |
FGFR2 S252W | endometrial carcinoma | sensitive | GSK3052230 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, GSK3052230 (FP-1039) treatment resulted in greater tumor growth inhibition (95% vs 30%) in cell line xenograft models of endometrial carcinoma harboring FGFR2 S252W compared to FGFR2 wild-type models (PMID: 23536011). | 23536011 |
FGFR2 S252W | endometrial cancer | sensitive | Derazantinib | Preclinical - Cell culture | Actionable | In a preclinical study, Derazantinib (ARQ 087) inhibited growth of endometrial cancer cells harboring FGFR2 S252W in culture (PMID: 27627808). | 27627808 |
FGFR2 S252W | Advanced Solid Tumor | predicted - sensitive | Pemigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 S252W were sensitive to treatment with Pemazyre (pemigatinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 S252W | endometrial cancer | sensitive | E7090 | Preclinical - Cell culture | Actionable | In a preclinical study, an endometrial cancer cell line harboring FGFR2 S252W (PMID: 18552176) demonstrated sensitivity to E7090 in culture, resulting in decreased cell viability (PMID: 27535969). | 18552176 27535969 |
FGFR2 S252W | Advanced Solid Tumor | predicted - sensitive | E7090 | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 S252W were sensitive to treatment with E7090 in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |