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| Gene Symbol | FGFR2 | ||||||||||
| Synonyms | BBDS | BEK | BFR-1 | CD332 | CEK3 | CFD1 | ECT1 | JWS | K-SAM | KGFR | TK14 | TK25 | ||||||||||
| Gene Description | FGFR2, fibroblast growth factor receptor 2, is a receptor tyrosine kinase activated upon binding of the FGF ligand, which activates RAS-MAPK and PI3K-AKT pathways (PMID: 22508544). Altered function of FGFR2 through activating mutations, fusions, and amplification increases cell proliferation and tumorigenesis (PMID: 22508544) and is observed in prostate (PMID: 30761180), breast, lung, uterine, and ovarian cancers (PMID: 29104507), while FGFR2 amplification (PMID: 31076567) and overexpression (PMID: 30662521) is commonly observed in gastric cancer. | ||||||||||
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| Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
|---|---|---|---|---|
| A264T | missense | gain of function - predicted | FGFR2 A264T lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). A264T results in proliferation similar to wild-type Fgfr2 in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| A314D | missense | unknown | FGFR2 A314D lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). A314D has been identified in sequencing studies (PMID: 18552176), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| A315C | missense | unknown | FGFR2 A315C lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). A315C has not been characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2023). | |
| A315S | missense | unknown | FGFR2 A315S lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). A315S results in altered affinity for Fgfr ligands in in vitro assays when combined with S252L (PMID: 15282208), but has not been characterized individually and therefore, its effect on Fgfr2 protein function is unknown. | |
| A315T | missense | unknown | FGFR2 A315T lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). A315T has been identified in the scientific literature (PMID: 17525745), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| A344G | missense | unknown | FGFR2 A344G lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). A344G has not been characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| A344P | missense | unknown | FGFR2 A344P lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). A344P has not been characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| A371V | missense | no effect - predicted | FGFR2 A371V lies within the extracellular domain of the Fgfr2 protein (UniProt.org). A371V results in proliferation similar to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type in cultured cells (PMID: 34272467), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| A389T | missense | unknown | FGFR2 A389T lies within the transmembrane domain of the Fgfr2 protein (UniProt.org). A389T results in proliferation similar to wild-type Fgfr2 in a competition assay (PMID: 34272467) and is not transforming in culture in one study (PMID: 18552176), but increased transformation activity in cultured cells in another study (PMID: 34272467), and therefore, its effect on Fgfr2 protein function is unknown. | |
| A553D | missense | unknown | FGFR2 A553D lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). A553D has been predicted to affect Fgfr2 protein stability by structural modeling (PMID: 32859654), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2023). | |
| A648T | missense | loss of function | FGFR2 A648T lies within the protein kinase domain of the Fgfr2 protein (PMID: 19147536). A648T confers a loss of function to the Fgfr2 protein demonstrated by decreased proliferation relative to wild-type Fgfr2 in a competition assay and decreased transformation activity (PMID: 34272467), decreaed protein kinase activity, and reduced downstream MAPK signaling pathway activation in cultured cells (PMID: 19147536). | |
| A67V | missense | gain of function - predicted | FGFR2 A67V lies within Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). A67V results in decreased proliferation relative to wild-type Fgfr2 in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| A97T | missense | unknown | FGFR2 A97T lies within Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). A97T has been identified in sequencing studies (PMID: 28581676, PMID: 18552176), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| act mut | unknown | gain of function | FGFR2 act mut indicates that this variant results in a gain of function in the Fgfr2 protein. However, the specific amino acid change has not been identified. | |
| amp | none | no effect | FGFR2 amp indicates an increased number of copies of the FGFR2 gene. However, the mechanism causing the increase is unspecified. | |
| C278F | missense | unknown | FGFR2 C278F lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). C278F results in increased Fgfr2 dimerization and autophosphorylation, however, also leads to rapid Fgfr2 degradation (PMID: 16844695), impaired Erk and Tgf-beta signaling, and decreased cell viability in culture (PMID: 20004243), and therefore, its effect on Fgfr2 protein function is unknown. | |
| C342F | missense | unknown | FGFR2 C342F lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). C342F has been identified in sequencing studies (PMID: 11781872), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| C342R | missense | gain of function - predicted | FGFR2 C342R lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). C342R results in constitutive activation of the Fgfr2 dimer state in an in vitro assay (PMID: 27596331), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| C342S | missense | unknown | FGFR2 C342S lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). C342S has not been characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| C342Y | missense | gain of function | FGFR2 C342Y lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). C342Y results in activation of Fgfr2 signaling as indicated by decreased differentiation and increased apoptosis in osteoblasts in culture and in transgenic animal models (PMID: 10851026, PMID: 15316116). | |
| C382R | missense | gain of function | FGFR2 C382R (also referred to as C383R) lies within the helical domain of the Fgfr2 protein (UniProt.org). C382R results in proliferation similar to wild-type Fgfr2 in a competition assay (PMID: 34272467), but confers a gain of function on the Fgfr2 protein, as demonstrated by constitutive MAPK pathway activation (PMID: 24993163), and transformation of cells in culture (PMID: 24993163, PMID: 34272467). | |
| C382Y | missense | no effect - predicted | FGFR2 C382Y lies within the helical domain of the Fgfr2 protein (UniProt.org). C382Y has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 in cultured cells (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| C383R | missense | gain of function - predicted | FGFR2 C383R (corresponds to C382R in the canonical isoform) lies within the transmembrane domain of the Fgfr2 protein (UniProt.org). C383R results in Fgfr2 autophosphorylation and transformation in culture (PMID: 9136983), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| C492F | missense | unknown | FGFR2 C492F (corresponds to C491F in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). C492F results in reduced Frs2 and Erk phosphorylation in the context of an FGFR2 fusion and confers resistance to FGFR inhibitors in the context of FGFR2-PHGDH in culture (PMID: 37843855), but has not been individually characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Oct 2023). | Y |
| C62Y | missense | gain of function - predicted | FGFR2 C62Y lies within Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). C62Y results in proliferation similar to wild-type Fgfr2 in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| D101Y | missense | gain of function | FGFR2 D101Y lies within the extracellular Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). D101Y results in a growth advantage relative to wild-type Fgfr2 in a competition assay (PMID: 34272467) and increased transformation activity in cultured cells (PMID: 34272467, PMID: 18552176). | |
| D138N | missense | unknown | FGFR2 D138N lies within the extracellular domain of the Fgfr2 protein (UniProt.org). D138N has been identified in the scientific literature (PMID: 17360555), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| D247Y | missense | unknown | FGFR2 D247Y lies within Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). D247Y has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Jan 2024). | |
| D283N | missense | unknown | FGFR2 D283N lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). D283N has been identified in sequencing studies (PMID: 16140923), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| D304N | missense | no effect - predicted | FGFR2 D304N lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). D304N has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 in cultured cells (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| D336N | missense | unknown | FGFR2 D336N lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). D336N has been identified in sequencing studies (PMID: 22810696, PMID: 26373574), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| D471N | missense | no effect - predicted | FGFR2 D471N lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). D471N results in proliferation similar to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type in cultured cells (PMID: 34272467), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| D479N | missense | unknown | FGFR2 D479N lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). D479N has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| D530N | missense | loss of function | FGFR2 D530N lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). D530N confers a loss of function on the Fgfr2 protein, as demonstrated by decreased protein kinase activity and reduced downstream MAPK signaling pathway activation, and decreased proliferation compared to wild-type Fgfr2 in cell culture (PMID: 19147536). | |
| D602E | missense | unknown | FGFR2 D602E lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). D602E has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| D650A | missense | gain of function - predicted | FGFR2 D650A lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). D650A demonstrates increased kinase activity compared to wild-type Fgfr2 in an in vitro assay (PMID: 28166054), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| D650G | missense | loss of function - predicted | FGFR2 D650G lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). D650G demonstrates decreased kinase activity compared to wild-type Fgfr2 in an in vitro assay (PMID: 28166054), and therefore, is predicted to lead to a loss of Fgfr2 protein function. | |
| D650I | missense | gain of function - predicted | FGFR2 D650I lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). D650I demonstrates increased kinase activity compared to wild-type Fgfr2 in an in vitro assay (PMID: 28166054), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| D650L | missense | gain of function - predicted | FGFR2 D650L lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). D650L demonstrates increased kinase activity compared to wild-type Fgfr2 in an in vitro assay (PMID: 28166054), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| D650V | missense | gain of function - predicted | FGFR2 D650V lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). D650V demonstrates increased kinase activity compared to wild-type Fgfr2 in an in vitro assay (PMID: 28166054), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| D650Y | missense | unknown | FGFR2 D650Y lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). D650Y has been demonstrated to confer resistance to Fgfr inhibitors as a secondary resistance mutation (PMID: 34250419), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| dec exp | none | no effect | FGFR2 dec exp indicates decreased expression of the Fgfr2 protein and/or mRNA. However, the mechanism causing the decreased expression is unspecified. | |
| del exon5 | deletion | unknown | FGFR2 del exon5 indicates a deletion of exon 5 of the FGFR2 gene. | |
| del exon7 | deletion | unknown | FGFR2 del exon7 indicates a deletion of exon 7 of the FGFR2 gene. | |
| dup exon9-17 | duplication | unknown | FGFR2 dup exon9-17 indicates a tandem duplication of exons 9-17 of the FGFR2 gene. | |
| E116K | missense | unknown | FGFR2 E116K lies within Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). E116K has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Mar 2024). | |
| E160A | missense | unknown | FGFR2 E160A lies within Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). E160A is predicted to disrupt Fgfr2-heparan sulfate interaction and Fgfr dimerization based on structural modeling (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| E160K | missense | gain of function - predicted | FGFR2 E160K lies within Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). E160K results in proliferation similar to wild-type Fgfr2 in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| E163K | missense | gain of function - predicted | FGFR2 E163K lies within Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). E163K results in proliferation similar to wild-type Fgfr2 in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| E219K | missense | unknown | FGFR2 E219K lies within Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). E219K is predicted to disrupt Fgf- and heparin-induced Fgfr2 dimerization based on structural modeling (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| E470Q | missense | unknown | FGFR2 E470Q lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). E470Q has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| E475K | missense | unknown | FGFR2 E475K lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). E475K results in proliferation similar to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type in cultured cells (PMID: 34272467), but demonstrates slightly increased Fgfr2 kinase activity, and also decreases protein stability and cell proliferation in culture (PMID: 19147536), and therefore, its effect on Fgfr2 protein function is unknown. | |
| E565A | missense | gain of function | 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). | Y |
| E565G | missense | gain of function | FGFR2 E565G lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E565G results in increased Fgfr2 autophosphorylation and substrate phosphorylation in in vitro kinase assays (PMID: 17803937). | |
| E566A | missense | gain of function | 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). | Y |
| E566G | missense | gain of function | FGFR2 E566G (corresponds to E565G in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E566G results in increased Fgfr2 kinase activity and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597). | Y |
| E574K | missense | unknown | FGFR2 E574K lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E574K has been identified in the scientific literature (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| E596K | missense | no effect - predicted | FGFR2 E596K lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E596K results in proliferation similar to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type in cultured cells (PMID: 34272467), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| E636* | nonsense | unknown | FGFR2 E636* results in the premature truncation of the Fgfr2 protein at amino acid 636 of 821 (UniProt.org). E636* has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Mar 2024). | |
| E636K | missense | unknown | FGFR2 E636K lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E636K is predicted to affect the kinase activity of Fgfr2 by structural modeling (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Mar 2024). | |
| E695K | missense | loss of function - predicted | FGFR2 E695K lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E695K results in decreased proliferation relative to wild-type Fgfr2 in a competition assay and decreased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a loss of Fgfr2 protein function. | |
| E718K | missense | gain of function - predicted | FGFR2 E718K lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E718K results in decreased proliferation relative to wild-type Fgfr2 in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| E731K | missense | unknown | FGFR2 E731K lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). E731K results in increased phosphorylation of Fgfr2, Erk signaling, and transcriptional activation of Runx2 in culture (PMID: 21928350), however in another study, results in cell proliferation and viability levels similar to wild-type Fgfr2 in two different cell lines (PMID: 29533785), and therefore, its effect on Fgfr2 protein function is unknown. | |
| E768* | nonsense | gain of function - predicted | FGFR2 E768* results in a premature truncation of the Fgfr2 protein at amino acid 768 of 821 (UniProt.org). E768* is predicted to lead to a gain of Fgfr2 protein function as a corresponding mouse variant (E673*) activates FGFR2 signaling and promotes colony formation in cell culture, and leads to tumor formation in a mouse model (PMID: 35948633). | |
| E777K | missense | unknown | FGFR2 E777K lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). E777K has been identified in sequencing studies (PMID: 29107334), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| exon 5 del | deletion | unknown | FGFR2 exon 5 deletions are in-frame deletions within the extracellular domain of the Fgfr2 protein (PMID: 33926920). | |
| exon 7 del | deletion | unknown | FGFR2 exon 7 deletions are in-frame deletions within the extracellular domain of the Fgfr2 protein (PMID: 33926920). | |
| exon5 | unknown | unknown | FGFR2 exon 5 indicates an unspecified mutation has occurred in exon 5 of the FGFR2 gene. | |
| exon7 | unknown | unknown | FGFR2 exon 7 indicates an unspecified mutation has occurred in exon 7 of the FGFR2 gene. | |
| F276C | missense | gain of function | FGFR2 F276C lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniPort.org). F276C results in increased Fgfr2 expression, altered cellular localization, and ligand-independent Erk phosphorylation in culture (PMID: 30761385). | |
| F276I | missense | unknown | FGFR2 F276I lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). F276I has not been characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Oct 2023). | |
| F276V | missense | unknown | FGFR2 F276V lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). F276V has been identified in sequencing studies (PMID: 24578066), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| F386_A389del | deletion | no effect - predicted | FGFR2 F386_A389del results in the deletion of four amino acids of the Fgfr2 protein from amino acids 386 to 389 (UniProt.org). F386_A389del has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 in cultured cells (PMID: 29533785), and therefore, it is predicted to have no effect on Fgfr2 protein function. | |
| fusion | fusion | unknown | FGFR2 fusion indicates a fusion of the FGFR2 gene, but the fusion partner is unknown. | |
| G183fs | frameshift | loss of function - predicted | FGFR2 G183fs results in a change in the amino acid sequence of the Fgfr2 protein beginning at aa 183 of 821, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), G183fs is predicted to lead to a loss of Fgfr2 protein function. | |
| G227E | missense | unknown | FGFR2 G227E lies within the Ig-like C2-type 2 domain of the Fgfr2 protein (UniProt.org). The functional effect of G227E is conflicting, as it has been reported to impair receptor processing and trafficking to the cell membrane and reduce ligand-dependent cell proliferation in one study (PMID: 19147536), similar cell proliferation and viability levels to wild-type Fgfr2 in two different cell lines in another study (PMID: 29533785), and a growth advantage relative to wild-type Fgfr2 in a competition assay but transformation activity similar to wild-type Fgfr2 in cultured cells (PMID: 34272467), and therefore, its effect on Fgfr2 protein function is unknown. | |
| G227R | missense | unknown | FGFR2 G227R lies within Ig-like C2-type domain 2 of the Fgfr2 protein (UniPort.org). G227R has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| G271E | missense | loss of function | FGFR2 G271E lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). G271E confers a loss of function to the Fgfr2 protein as indicated by impaired receptor processing and decreased cell proliferation as compared to wild-type Fgfr2 in culture (PMID: 19147536). | |
| G272V | missense | unknown | FGFR2 G272V lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). G272V has been identified in the scientific literature (PMID: 20106510), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| G302W | missense | unknown | FGFR2 G302W lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). G302W has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| G305R | missense | no effect - predicted | FGFR2 G305R lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). G305R results in proliferation similar to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type in cultured cells (PMID: 34272467), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| G338R | missense | unknown | FGFR2 G338R lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). G338R has not been characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Mar 2024). | |
| G364E | missense | gain of function - predicted | FGFR2 G364E lies within the extracellular domain of the Fgfr2 protein (UniProt.org). G364E results in decreased proliferation in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| G384E | missense | unknown | FGFR2 G384E lies within the transmembrane domain of the Fgfr2 protein (UniProt.org). G384E has been identified in sequencing studies (PMID: 27147599), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| G462E | missense | unknown | FGFR2 G462E lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). G462E has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| G542A | missense | unknown | FGFR2 G542A lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). G542A has been identified in the scientific literature (PMID: 38267212), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Feb 2024). | |
| G542E | missense | loss of function - predicted | FGFR2 G542E lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). G542E results in decreased proliferation relative to wild-type Fgfr2 in a competition assay and decreased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a loss of Fgfr2 protein function. | |
| G583R | missense | unknown | FGFR2 G583R lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). G583R has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| G583V | missense | unknown | FGFR2 G583V lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). G583V has been identified in sequencing studies (PMID: 22980975, PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| G583W | missense | unknown | FGFR2 G583W lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). G583W has been identified in sequencing studies (PMID: 22960745, PMID: 24836576), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| G613S | missense | no effect - predicted | FGFR2 G613S lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). G613S results in proliferation similar to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type in cultured cells (PMID: 34272467), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| G663E | missense | gain of function | FGFR2 G663E lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). G663E results in increased Fgfr2 autophosphorylation and substrate phosphorylation in in vitro kinase assays (PMID: 17803937). | |
| G690R | missense | unknown | FGFR2 G690R lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). G690R has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| G701S | missense | unknown | FGFR2 G701S lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). G701S is predicted to inhibit Fgfr2 kinase activity indirectly by structural modeling (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| H167_N173del | deletion | gain of function | FGFR2 H167_N173del results in the deletion of seven amino acids in Ig-like C2-type domain 2 of the Fgfr2 protein from amino acids 167 to 173 (UniProt.org). H167_N173del results in cell transformation (J Clin Oncol 38, 2020 (suppl 4; abstr 567), PMID: 33926920), increased proliferation, invasion, and migration (PMID: 37964396), anchorage-independent growth, constitutive activation of Fgfr2 kinase activity in culture, and tumor formation in an in vivo model (PMID: 33926920). | |
| H213Y | missense | unknown | FGFR2 H213Y lies within Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). H213Y is predicted to disrupt the interaction of Fgfr2 with heparan sulfate based on structural modeling (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| H242Y | missense | no effect - predicted | FGFR2 H242Y lies within Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). H242Y results in proliferation similar to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type in cultured cells (PMID: 34272467), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| H416R | missense | gain of function - predicted | FGFR2 H416R lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). H416R results in proliferation similar to wild-type Fgfr2 in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| H544Q | missense | gain of function - predicted | FGFR2 H544Q lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). H544Q results in proliferation similar to wild-type Fgfr2 in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| H683L | missense | unknown | FGFR2 H683L (corresponds to H682L in the canonical isoform) lies within the protein kinase domain of the FGFR2 protein (UniProt.org). H683L has been associated with resistance to Fgfr inhibitors in the context of an FGFR2 fusion in culture (PMID: 31109923), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Oct 2023). | Y |
| I288_D304del | deletion | gain of function - predicted | FGFR2 I288_D304del results in the deletion of 17 amino acids in Ig-like C2-type domain 3 of the Fgfr2 protein from amino acids 288 to 304 (UniProt.org). I288_D304del results in increased proliferation, migration, and invasion in cultured cells (PMID: 37964396), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| I288_E295delinsT | indel | unknown | FGFR2 I288_E295delinsT results in deletion of eight amino acids in Ig-like C2-type domain 3 of the Fgfr2 protein from amino acids 288 to 295, combined with the insertion of a threonine (T) at the same location (UniProt.org). I288_E295delinsT has been identified in the scientific literature (PMID: 33926920), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| I291_Y308del | deletion | unknown | FGFR2 I291_Y308del results in the deletion of eighteen amino acids in the Fgfr2 protein from amino acids 291 to 308 (UniProt.org). I291_Y308del has been identified in the scientific literature (Cancer Res (2023) 83 (8_Supplement): CT016), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| I380V | missense | unknown | FGFR2 I380V lies within the transmembrane domain of the Fgfr2 protein (UniProt.org). I380V has been identified in sequencing studies (PMID: 18948947), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Mar 2024). | |
| I422V | missense | gain of function - predicted | FGFR2 I422V lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). I422V results in proliferation similar to wild-type Fgfr2 in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| I547D | missense | unknown | FGFR2 I547D lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). I547D has been identified in sequencing studies (PMID: 22383975), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| I547V | missense | gain of function | FGFR2 I547V lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). I547V results in elevated kinase activity compared to wild-type Fgfr2 protein in substrate phosphorylation assays (PMID: 28166054, PMID: 31959966) in cultured cells. | |
| I548V | missense | gain of function | FGFR2 I548V lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). I548V confers a gain of function on the Fgfr2 protein, as demonstrated by increased Fgfr2 kinase activity and enhanced cell proliferation in the presence of ligand in cell culture (PMID: 23908597). | |
| I548Wfs*8 | frameshift | gain of function - predicted | FGFR2 I548Wfs*8 indicates a shift in the reading frame starting at amino acid 548 and terminating 8 residues downstream causing a premature truncation of the 821 amino acid Fgfr2 protein (UniProt.org). I548Wfs*8 results in increased proliferation and invasion in cultured cells (PMID: 37964396), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| I590M | missense | unknown | FGFR2 I590M lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). I590M has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| I642T | missense | unknown | FGFR2 I642T lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). I642T has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| I642V | missense | loss of function | FGFR2 I642V lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). I642V confers a loss of function on the Fgfr2 protein, as demonstrated by decreased protein kinase activity and reduced downstream MAPK signaling pathway activation and decreased proliferation compared to wild-type Fgfr2 in cell culture (PMID: 19147536). | |
| inact mut | unknown | loss of function | FGFR2 inact mut indicates that this variant results in a loss of function of the Fgfr2 protein. However, the specific amino acid change has not been identified. | |
| K292M | missense | no effect - predicted | FGFR2 K292M lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). K292M has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 in cultured cells (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| K310R | missense | gain of function - predicted | FGFR2 K310R lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). K310R results in proliferation similar to wild-type Fgfr2 in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| K405E | missense | unknown | FGFR2 K405E lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). K405E has been identified in sequencing studies (PMID: 25669975), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| K41E | missense | no effect - predicted | FGFR2 K41E lies within Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). K41E results in decreased Fgfr2 expression, but demonstrates subcellular localization, basal and ligand-dependent Erk phosphorylation levels similar to wild-type Fgfr2 in culture (PMID: 30761385), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| K420I | missense | unknown | FGFR2 K420I lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). K420I has been identified in sequencing studies (PMID: 25035393), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| K517R | missense | loss of function | FGFR2 K517R lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K517R results in decreased Fgfr2 kinase activity and inhibited cell proliferation in culture (PMID: 19147536). | |
| K525E | missense | gain of function | FGFR2 K525E (corresponds to K641E in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K525E results in increased Fgfr2 autophosphorylation and substrate phosphorylation in in vitro kinase assays (PMID: 17803937). | |
| K526E | missense | gain of function - predicted | FGFR2 K526E lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K526E results in increased Fgfr2 autophosphorylation in an in vitro assay (PMID: 17803937), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| K545del | deletion | gain of function - predicted | FGFR2 K545del results in the deletion of an amino acid in the protein kinase domain of the Fgfr2 protein at amino acid 545 (UniProt.org). K545del results in increased proliferation, migration, and invasion in 2 of 3 cell lines in culture (PMID: 37964396), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| K641N | missense | gain of function | FGFR2 K641N lies within the protein kinase domain of the Fgfr2b protein (UniProt.org). K641N (reported as K642N) results in increased Fgfr2 kinase activity and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597). | |
| K641R | missense | gain of function | FGFR2 K641R lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K641R results in increased Fgfr2 autophosphorylation and activation of Mek1/2, Stat3 signaling in cell culture (PMID: 23527311). | |
| K642R | missense | gain of function | FGFR2 K642R (corresponds to K641R in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K642R confers a gain of function to the Fgfr2 protein, as demonstrated by increased autophosphorylation, increased phosphorylation of FRS2, and increased activation of Mek1/2 and Stat3, upon FGF1 stimulation, and as compared to wild-type Fgfr2 in cell culture (PMID: 23527311). | |
| K659E | missense | gain of function | FGFR2 K659E (also referred to as K660E from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K659E results in a growth advantage relative to wild-type Fgfr2 in a competition assay and increased transformation activity in cultured cells (PMID: 34272467), increased phosphorylation of downstream signaling molecules, induces colony formation in culture (PMID: 23786770), and results in the ability to induce senescence and cooperate with Myc to induce transformation of cell lines in culture (PMID: 19403560). | |
| K659M | missense | gain of function - predicted | FGFR2 K659M (also referred to as K660M from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K659M results in increased kinase activity compared to wild-type Fgfr2 in substrate phosphorylation assays (PMID: 28166054), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| K659N | missense | gain of function | FGFR2 K659N (also referred to as K660N from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K659N results in proliferation similar to wild-type Fgfr2 in a competition assay (PMID: 34272467) but confers a gain of function to the Fgfr2 protein as demonstrated by increased autophosphorylation and phosphorylation of downstream targets, Mek and Stat3 (PMID: 23527311), and increased transformation activity in cultured cells (PMID: 34272467). | |
| K659Q | missense | unknown | FGFR2 K659Q lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K659Q has been demonstrated to confer resistance to Fgfr inhibitors as a secondary resistance mutation (PMID: 34250419), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2023). | Y |
| K660E | missense | gain of function | FGFR2 K660E (corresponds to K659E in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K660E results in increased phosphorylation of Fgfr2, activation of downstream signaling, and is transforming in cell culture (PMID: 23786770). | Y |
| K660M | missense | unknown | FGFR2 K660M (corresponds to K659M in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K660M has been associated with resistance to Fgfr inhibitors in the context of an FGFR2 fusion (PMID: 31109923), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Mar 2024). | Y |
| K660N | missense | gain of function | FGFR2 K660N (corresponds to K559N in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K660N confers a gain of function to the Fgfr2 protein, as demonstrated by increased autophosphorylation, increased phosphorylation of FRS2, and increased activation of Mek1/2 and Stat3, upon FGF1 stimulation, and as compared to wild-type Fgfr2 in cell culture (PMID: 23527311). | |
| K714R | missense | unknown | FGFR2 K714R (also referred to as K715R from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K714R may be associated with resistance to Fgfr inhibitors, as the corresponding K715R variant in isoform IIIb has been associated with resistance to Fgfr inhibition in the context of an FGFR2 fusion (PMID: 31109923), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Mar 2024). | |
| K715R | missense | unknown | FGFR2 K715R (corresponds to K714R in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K715R has been associated with resistance to Fgfr inhibitors in the context of an FGFR2 fusion (PMID: 31109923), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Mar 2024). | Y |
| L258F | missense | no effect - predicted | FGFR2 L258F lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). L258F has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 in cultured cells (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| L33S | missense | unknown | FGFR2 L33S lies within Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). L33S results in decreased proliferation in a competition assay but transformation activity similar to wild-type Fgfr2 in cultured cells (PMID: 34272467), and therefore, its effect on Fgfr2 protein function is unknown. | |
| L397M | missense | unknown | FGFR2 L397M lies within the transmembrane domain of the Fgfr2 protein (UniProt.org). L397M has been identified in sequencing studies (PMID: 22383975), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| L550F | missense | unknown | FGFR2 L550F lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L550F has been demonstrated to confer resistance to Fgfr inhibitors as a secondary resistance mutation (PMID: 34250419), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2023). | Y |
| L551F | missense | unknown | FGFR2 L551F lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L551F has been associated with resistance to some FGFR inhibitors in cell culture (PMID: 37377403), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Feb 2024). | Y |
| L551I | missense | unknown | FGFR2 L551I lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L551I has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| L552F | missense | unknown | FGFR2 L552F (corresponds to L551F in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L552F has been identified in the scientific literature (PMID: 37843855, PMID: 36089135), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Oct 2023). | |
| L560F | missense | gain of function - predicted | FGFR2 L560F lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L560F results in proliferation similar to wild-type Fgfr2 in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| L617F | missense | unknown | FGFR2 L617F lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). The functional effect of L617F is conflicting, as it results in enhanced Fgfr2 autophosphorylation, activation of Runx2 (PMID: 23913723), and increased substrate phosphorylation (PMID: 28166054), but activation of Mapk/Erk was similar to wild-type Fgfr2 in cell culture (PMID: 23913723) and therefore, its effect on Fgfr2 protein function is unknown. | |
| L617M | missense | unknown | FGFR2 L617M lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L617M has been demonstrated to confer resistance to FGFR inhibitors as a secondary resistance mutation in the context of FGFR2 fusions (PMID: 31911531), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Oct 2023). | Y |
| L617V | missense | gain of function - predicted | FGFR2 L617V (also referred to as V618V from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L617V has been shown to confer resistance to Fgfr inhibitors in cell culture (PMID: 28034880), and demonstrates increased Fgfr2 kinase activity compared to wild-type in an in vitro assay (PMID: 28166054), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | Y |
| L618F | missense | unknown | FGFR2 L618F (corresponds to L617F in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L618F in combination with FGFR2 H167_N173del results in constitutive FGFR2 signaling in culture, and has been shown to be associated with secondary resistance to FGFR inhibitors (PMID: 33926920), but has not been individually characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | Y |
| L618M | missense | gain of function | FGFR2 L618M (corresponds to L617M in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L618M results in increased Fgfr2 kinase activity, enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597), and elevated kinase activity compared to wild-type Fgfr2 protein in substrate phosphorylation assays (PMID: 28166054). | |
| L618V | missense | gain of function - predicted | FGFR2 L618V (corresponds to L617V in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L618V has been shown to confer resistance to Fgfr inhibitors in cell culture (PMID: 28034880) and demonstrates increased Fgfr2 kinase activity compared to wild-type in an in vitro assay (PMID: 28166054), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | Y |
| L634V | missense | unknown | FGFR2 L634V (corresponds to L633V in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L634V has been identified in the scientific literature (PMID: 37843855, PMID: 36089135), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Oct 2023). | |
| L761Tfs*55 | frameshift | unknown | FGFR2 L761Tfs*55 indicates a shift in the reading frame starting at amino acid 761 and terminating 55 residues downstream causing a premature truncation of the 821 amino acid Fgfr2 protein (UniProt.org). L761Tfs*55 results in increased transformation ability in one of two different cell lines (PMID: 29533785), but has not been fully biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown. | |
| L770V | missense | unknown | FGFR2 L770V lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L770V is predicted to decrease phospholipase C-gamma activation by Fgfr2 based on structural modeling (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| L772F | missense | unknown | FGFR2 L772F lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). L772F has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2023). | |
| L776Rfs*6 | frameshift | gain of function - predicted | FGFR2 L776Rfs*6 indicates a shift in the reading frame starting at amino acid 776 and terminating six residues downstream causing a premature truncation of the 821 amino acid Fgfr2 protein (UniProt.org). L776Rfs*6 is predicted to lead to a gain of Fgfr2 protein function as a corresponding mouse variant (L681Rfs*6) promotes colony formation in cell culture and leads to tumor formation in a mouse model (PMID: 35948633). | |
| M121V | missense | unknown | FGFR2 M121V lies within Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). M121V has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| M186T | missense | loss of function - predicted | FGFR2 M186T lies within Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). M186T is a common Fgfr2 polymorphism (PMID: 11781872, PMID: 25129254) that results in similar cell proliferation and viability levels as wild-type Fgfr2 (PMID: 29533785), and proliferation similar to wild-type in a competition assay, but decreased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a loss of Fgfr2 protein function. | |
| M391R | missense | unknown | FGFR2 M391R lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). The functional effect of M391R is conflicting, as it has been reported to result in increased nucleolar Fgfr2 activity and cell proliferation in one study (PMID: 24908667), but results in similar cell proliferation and viability levels to wild-type Fgfr2 in two different cell lines in another study (PMID: 29533785), and therefore, its effect on Fgfr2 protein function is unknown. | |
| M535T | missense | unknown | FGFR2 M535T lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M535T has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| M536I | missense | gain of function | FGFR2 M536I (corresponds to M535I in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M536I results in increased Fgfr2 kinase activity and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597). | |
| M537A | missense | loss of function - predicted | FGFR2 M537A lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M537A demonstrates decreased kinase activity compared to wild-type Fgfr2 in an in vitro assay (PMID: 28166054), and therefore, is predicted to lead to a loss of Fgfr2 protein function. | |
| M537I | missense | gain of function - predicted | FGFR2 M537I (also referred to as M538I from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M537I results in elevated kinase activity compared to wild-type Fgfr2 protein in substrate phosphorylation assays (PMID: 28166054), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| M538I | missense | gain of function | FGFR2 M538I (corresponds to M537I in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M538I confers a gain of function to the Fgfr2 protein as demonstrated by increased Fgfr2 kinase activity (PMID: 32723837, PMID: 23908597) and enhanced cell proliferation in the presence of ligand in cell culture (PMID: 23908597), and has been associated with decreased sensitivity to some FGFR inhibitors (PMID: 23908597). | |
| M538L | missense | unknown | FGFR2 M538L lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M538L has been identified as a secondary resistance mutation in the context of an FGFR2 fusion (PMID: 34250419), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| M538R | missense | unknown | FGFR2 M538R lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M538R has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| M539L | missense | unknown | FGFR2 M539L (corresponds to M538L in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M539L has been identified in the scientific literature (PMID: 37843855, PMID: 36089135), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Oct 2023). | |
| M540A | missense | loss of function - predicted | FGFR2 M540A lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M540A demonstrates decreased kinase activity compared to wild-type Fgfr2 in an in vitro assay (PMID: 28166054), and therefore, is predicted to lead to a loss of Fgfr2 protein function. | |
| M584V | missense | unknown | FGFR2 M584V lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M584V has been identified in sequencing studies (PMID: 22960745), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| M640I | missense | no effect - predicted | FGFR2 M640I lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M640I results in proliferation similar to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type in cultured cells (PMID: 34272467), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| M722I | missense | loss of function - predicted | FGFR2 M722I lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). M722I results in decreased proliferation relative to wild-type Fgfr2 in a competition assay and decreased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a loss of Fgfr2 protein function. | |
| mutant | unknown | unknown | FGFR2 mutant indicates an unspecified mutation in the FGFR2 gene. | |
| N211I | missense | unknown | FGFR2 N211I lies within Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). N211I has been identified in sequencing studies (PMID: 18552176), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| N549D | missense | gain of function - predicted | FGFR2 N549D lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N549D results in proliferation similar to wild-type Fgfr2 in a competition assay but increased transformation activity in cultured cells (PMID: 34272467) and has been associated with resistance to Fgfr inhibitors in the context of an FGFR2 fusion in culture (PMID: 28034880), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | Y |
| N549H | missense | gain of function | FGFR2 N549H lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N549H demonstrates resistance to FGFR inhibitors in the context of FGFR2-CLIP1 in culture (PMID: 31371345), and confers a gain of function to the Fgfr2 protein as indicated by disengagement of autoinhibitory mechanisms thereby resulting in constitutive activation and downstream pathway activation (PMID: 17525745, PMID: 17803937), elevated kinase activity in substrate phosphorylation assays (PMID: 28166054), a growth advantage relative to wild-type Fgfr2 in a competition assay, and increased transformation activity in cultured cells (PMID: 34272467). | Y |
| N549K | missense | gain of function | FGFR2 N549K lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N549K confers a gain of function to the Fgfr2 protein resulting in a growth advantage relative to wild-type Fgfr2 in a competition assay, increased transformation activity in cultured cells (PMID: 34272467), oncogenic transformation in culture (PMID: 18552176, PMID: 17803937, PMID: 29533785) and increased MAPK pathway signaling in cultured cells (PMID: 19147536). | Y |
| N549S | missense | gain of function | FGFR2 N549S lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N549S demonstrates increased transforming activity compared to wild-type Fgfr2 in culture (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| N549T | missense | gain of function | FGFR2 N549T lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N549T results in increased Fgfr2 autophosphorylation and substrate phosphorylation in in vitro kinase assays (PMID: 17803937). | |
| N550D | missense | unknown | FGFR2 N550D (corresponds to N549D in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N550D has been identified in the scientific literature (PMID: 37843855), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Oct 2023). | |
| N550H | missense | gain of function | FGFR2 N550H (corresponds to N549H in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N550H results in increased Fgfr2 kinase activity, as well as increased Fgfr2 phosphorylation and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597). | Y |
| N550K | missense | gain of function | FGFR2 N550K (corresponds to N549K in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N550K results in increased Fgfr2 kinase activity (PMID: 32723837, PMID: 23908597) and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597). | |
| N550S | missense | gain of function | FGFR2 N550S lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N550S results in increased Fgfr2 kinase activity and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597). | |
| N550T | missense | gain of function | FGFR2 N550T (corresponds to N549T in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N550T results in increased Fgfr2 kinase activity and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597). | |
| N631_M640del | deletion | gain of function - predicted | FGFR2 N631_M640del results in the deletion of 10 amino acids in the protein kinase domain of the Fgfr2 protein from amino acids 631 to 640 (UniProt.org). N631_M640del results in increased proliferation, migration, and invasion in cultured cells (PMID: 37964396), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| N652S | missense | unknown | FGFR2 N652S lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N652S has been demonstrated to confer resistance to Fgfr inhibitors as a secondary resistance mutation (PMID: 34250419), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2023). | Y |
| N82K | missense | gain of function - predicted | FGFR2 N82K lies within Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). N82K results in proliferation similar to wild-type Fgfr2 in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| over exp | none | no effect | FGFR2 over exp indicates an over expression of the Fgfr2 protein and/or mRNA. However, the mechanism causing the over expression is unspecified. | |
| P253L | missense | gain of function - predicted | FGFR2 P253L lies within the extracellular domain of the Fgfr2 protein (UniProt.org). P253L does not confer growth advantage over wild-type Fgfr2 in a competition assay, but results in increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| P253R | missense | gain of function - predicted | FGFR2 P253R lies within the extracellular domain of the Fgfr2 protein (UniProt.org). P253R results in transformation activity similar to wild-type Fgfr2 in one study (PMID: 34272467), but a growth advantage relative to wild-type Fgfr2 in a competition assay (PMID: 34272467), loss of ligand specificity, activation of the p38/MAPK pathway in transgenic mouse models, and is transforming in cell culture (PMID: 11121055, PMID: 20175913, PMID: 23786770), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| P253S | missense | unknown | FGFR2 P253S lies within the extracellular domain of the Fgfr2 protein (UniProt.org). P253S has been identified in sequencing studies (PMID: 11781872), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| P256S | missense | unknown | FGFR2 P256S lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). P256S has been identified in sequencing studies (PMID: 25669975), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| P286S | missense | unknown | FGFR2 P286S lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). P286S has been identified in sequencing studies (PMID: 27103312), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2023). | |
| P303L | missense | no effect - predicted | FGFR2 P303L lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniPort.org). P303L results in proliferation similar to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type in cultured cells (PMID: 34272467), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| P582L | missense | no effect - predicted | FGFR2 P582L lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). P582L results in proliferation similar to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type in cultured cells (PMID: 34272467), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| P708S | missense | loss of function - predicted | FGFR2 P708S lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). P708S results in decreased proliferation relative to wild-type Fgfr2 in a competition assay and decreased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a loss of Fgfr2 protein function. | |
| P775L | missense | unknown | FGFR2 P775L lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). P775L has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| P781* | nonsense | gain of function - predicted | FGFR2 P781* results in a premature truncation of the Fgfr2 protein at amino acid 781 of 821 (UniProt.org). P781* is predicted to lead to a gain of Fgfr2 protein function as a corresponding mouse variant (P686*) promotes colony formation in cell culture and leads to tumor formation in a mouse model (PMID: 35948633). | |
| positive | unknown | unknown | FGFR2 positive indicates the presence of the FGFR2 gene, mRNA, and/or protein. | |
| Q212K | missense | gain of function - predicted | FGFR2 Q212K lies within Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). Q212K results in proliferation similar to wild-type Fgfr2 in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| Q259* | nonsense | loss of function - predicted | FGFR2 Q259* results in a premature truncation of the Fgfr2 protein at amino acid 259 of 821 (UniProt.org). Q259* results in similar cell proliferation and viability levels as wild-type Fgfr2 in two different cell lines (PMID: 29533785), but decreased proliferation relative to wild-type Fgfr2 in a competition assay and decreased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a loss of Fgfr2 protein function. | |
| Q289P | missense | unknown | FGFR2 Q289P lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). Q289P has been identified in sequencing studies (PMID: 19066959, PMID: 16526917), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| Q620K | missense | unknown | FGFR2 Q620K lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). Q620K has been identified in sequencing studies (PMID: 25035393, PMID: 29106415), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| Q746L | missense | unknown | FGFR2 Q746L lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). Q746L has been demonstrated to confer resistance to Fgfr inhibitors as a secondary resistance mutation (PMID: 34250419), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2023). | Y |
| R165W | missense | unknown | FGFR2 R165W lies within Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). R165W has been identified in sequencing studies (PMID: 27147599), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| R178C | missense | unknown | FGFR2 R178C lies within Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). R178C has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Oct 2023). | |
| R203C | missense | gain of function | FGFR2 R203C lies within the Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). R203C results in proliferation similar to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type in cultured cells (PMID: 34272467), but confers a gain of function to the Fgfr2 protein, as demonstrated by increased autophosphorylation, increased phosphorylation of FRS2, and increased activation of Mek1/2 and Stat3 upon FGF1 stimulation in cell culture (PMID: 23527311). | |
| R203H | missense | unknown | FGFR2 R203H lies within Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). R203H results in decreased proliferation relative to wild-type Fgfr2 in a competition assay but transformation activity similar to wild-type in cultured cells (PMID: 34272467), and therefore, its effect on Fgfr2 protein function is unknown. | |
| R210Q | missense | unknown | FGFR2 R210Q lies within Ig-like C2-type domain 2 of the Fgfr2 protein (UniProt.org). R210Q results in decreased proliferation relative to wild-type Fgfr2 in a competition assay but transformation activity similar to wild-type in cultured cells (PMID: 34272467), and therefore, its effect on Fgfr2 protein function is unknown. | |
| R251* | nonsense | loss of function - predicted | FGFR2 R251* results in a premature truncation of the Fgfr2 protein at amino acid 251 of 821 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), R251* is predicted to lead to a loss of Fgfr2 protein function. | |
| R251Q | missense | loss of function | FGFR2 R251Q lies within the region linking Ig-like domains II and III of the Fgfr2 protein (PMID: 11121055). R251Q results in proliferation similar to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type in cultured cells (PMID: 34272467), but confers a loss of function on the Fgfr2 protein as demonstrated by loss of ligand binding and diminished Mapk activation upon Fgf2 stimulation in cell culture (PMID: 19147536). | |
| R255Q | missense | loss of function - predicted | FGFR2 R255Q lies within the extracellular domain of the Fgfr2 protein (UniProt.org). R255Q results in decreased activation of Fgfr2 downstream signaling upon Fgf2 stimulation in culture (PMID: 27323706), and therefore, is predicted to lead to a loss of Fgfr2 protein function. | |
| R255W | missense | unknown | FGFR2 R255W lies within the extracellular domain of the Fgfr2 protein (UniProt.org). R255W has been identified in sequencing studies (PMID: 37964396, PMID: 37682528), but has not been biochemically characterized and therefore, its effect on Fgfr3 protein function is unknown (PubMed, Nov 2023). | |
| R330W | missense | no effect - predicted | FGFR2 R330W lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). R330W results in proliferation similar to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type in cultured cells (PMID: 34272467), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| R399* | nonsense | loss of function - predicted | FGFR2 R399* results in a premature truncation of the Fgfr2 protein at amino acid 399 of 821 (UniProt.org). R399* results in decreased proliferation relative to wild-type Fgfr2 in a competition assay and decreased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a loss of Fgfr2 protein function. | |
| R399Q | missense | gain of function - predicted | FGFR2 R399Q lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). R399Q results in proliferation similar to wild-type Fgfr2 in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| R625Q | missense | loss of function - predicted | FGFR2 R625Q lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). R625Q results in decreased proliferation compared to wild-type Fgfr2 in a competition assay and decreased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a loss of Fgfr2 protein function. | |
| R625T | missense | unknown | FGFR2 R625T lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). R625T has been identified in sequencing studies (PMID: 17344846), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| R664W | missense | unknown | FGFR2 R664W lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). R664W results in a growth advantage relative to wild-type Fgfr2 in a competition assay but transformation activity similar to wild-type in cultured cells (PMID: 34272467), and decreased autophosphorylation compared to wild-type Fgfr2 in an in vitro kinase assay (PMID: 28151998), and therefore, its effect on Fgfr2 protein function is unknown. | |
| R678G | missense | gain of function | FGFR2 R678G lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). R678G results in increased Fgfr2 autophosphorylation and substrate phosphorylation in in vitro kinase assays (PMID: 17803937). | |
| R6P | missense | no effect - predicted | FGFR2 R6P does not lie within any known functional domains of the Fgfr2 protein (UniProt.org). R6P results in proliferation similar to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type in cultured cells (PMID: 34272467), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| R759Q | missense | unknown | FGFR2 R759Q lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). R759Q is predicted to disrupt Fgfr2 kinase activity based on structural modeling (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Mar 2024). | |
| rearrange | unknown | unknown | FGFR2 rearrangement indicates an unspecified rearrangement of the FGFR2 gene. | |
| S24F | missense | unknown | FGFR2 S24F lies within the extracellular domain of the Fgfr2 protein (UniProt.org). S24F has been identified in the scientific literature (PMID: 31453370), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| S252F | missense | unknown | FGFR2 S252F lies within the extracellular domain of the Fgfr2 protein (UniProt.org). S252F has been identified in sequencing studies (PMID: 16418739), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| S252L | missense | unknown | FGFR2 S252L lies within the extracellular domain of the Fgfr2 protein (UniProt.org). S252L results in altered affinity for Fgfr ligands in in vitro assays when combined with A315S (PMID: 15282208), but has not been characterized individually and therefore, its effect on Fgfr2 protein function is unknown. | |
| S252W | missense | unknown | FGFR2 S252W lies within the extracellular domain of the Fgfr2 protein (UniProt.org). The functional effect of S252W is conflicting as it results in loss of ligand specificity, increased Fgfr2 activation, increased FGF7-stimulated shedding of HB-EGF, and is transforming in cell culture (PMID: 11121055, PMID: 18552176, PMID: 37759450) but results in a growth advantage relative to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type Fgfr2 in cultured cells in another study (PMID: 34272467), and therefore, its effect on Fgfr2 protein function is unknown. | |
| S267P | missense | unknown | FGFR2 S267P lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). S267P has been identified in sequencing studies (PMID: 11325814), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| S267_D273dup | duplication | gain of function | FGFR2 S267_D273dup (also referred to as A266_S267insSTVVGGD) indicates the insertion of seven duplicate amino acids, serine (S)-267 through aspartic acid (D)-273, in Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). S267_D273dup confers a gain of function on Fgfr2 as demonstrated by ligand-independent phosphorylation, dimerization, and oncogenic cell transformation (PMID: 26048680). | |
| S347C | missense | unknown | FGFR2 S347C lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). S347C has been identified in sequencing studies (PMID: 12544231), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| S354C | missense | gain of function | FGFR2 S354C lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). S354C confers a gain of function to the Fgfr2 protein, as demonstrated by increased transactivation of Runx2, increased autophosphorylation, and increased Erk1/2 phosphorylation, as compared to wild-type in in vitro assays (PMID: 23913723). | |
| S372C | missense | gain of function - predicted | FGFR2 S372C lies within the extracellular domain of the Fgfr2 protein (PMID: 17525745). S372C (also reported as S373C) results in constitutive dimerization of the receptor (PMID: 17525745), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| S372F | missense | unknown | FGFR2 S372F lies within the extracellular domain of the Fgfr2 protein (Uniprot.org). S372F has been identified in sequencing studies (PMID: 27892470), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2023). | |
| S436F | missense | no effect - predicted | FGFR2 S436F lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). S436F has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 in cultured cells (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| S57L | missense | unknown | FGFR2 S57L lies within Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). S57L has been identified in sequencing studies (PMID: 31874108, PMID: 31470906, PMID: 28524162), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Mar 2024). | |
| S587C | missense | unknown | FGFR2 S587C lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). S587C has been identified in the scientific literature (PMID: 23000897), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| S688F | missense | unknown | FGFR2 S688F lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). S688F has been identified in the scientific literature (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| S780A | missense | gain of function - predicted | FGFR2 S780A lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). S780A results in sustained Fgfr2 phosphorylation and faster cell migration in response to Fgf1 in cell culture (PMID: 31146385), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| S780D | missense | gain of function - predicted | FGFR2 S780D lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). S780D results in sustained Fgfr2 phosphorylation in response to Fgf1 in cell culture (PMID: 31146385), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| S780L | missense | gain of function - predicted | FGFR2 S780L lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). S780L results in sustained Fgfr2 phosphorylation and faster cell migration in response to Fgf1 in cell culture (PMID: 31146385), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| S782Rfs*3 | frameshift | gain of function - predicted | FGFR2 S782Rfs*3 indicates a shift in the reading frame starting at amino acid 776 and terminating 6 residues downstream causing a premature truncation of the 821 amino acid Fgfr2 protein (UniProt.org). S782Rfs*3 is predicted to lead to a gain of Fgfr2 protein function as a corresponding mouse variant (S687Rfs*3) promotes colony formation in cell culture and leads to tumor formation in a mouse model (PMID: 35948633). | |
| S789* | nonsense | gain of function - predicted | FGFR2 S789* results in a premature truncation of the Fgfr2 protein at amino acid 789 of 821 (UniProt.org). S789* is predicted to lead to a gain of Fgfr2 protein function as a corresponding mouse variant (S694*) promotes colony formation in cell culture and leads to tumor formation in a mouse model (PMID: 35948633). | |
| S791T | missense | gain of function - predicted | FGFR2 S791T lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). S791T results in proliferation similar to wild-type Fgfr2 in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| S792Ffs*4 | frameshift | unknown | FGFR2 S792Ffs*4 indicates a shift in the reading frame starting at amino acid 792 and terminating four residues downstream causing a premature truncation of the 821 amino acid Fgfr2 protein (UniProt.org). S792Ffs*4 (corresponding to S697Ffs*4 in a mouse isoform) leads to limited increase in FGFR2 signaling and colony formation in cell culture but promotes tumor formation in a mouse model (PMID: 35948633), and therefore, its effect on Fgfr2 protein function is unknown. | |
| S799A | missense | no effect - predicted | FGFR2 S799A does not lie within any known functional domains of the Fgfr2 protein (UniProt.org). S799A has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 in cultured cells (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| T319I | missense | unknown | FGFR2 T319I lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). T319I has been identified in sequencing studies (PMID: 37916958), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Jan 2024). | |
| T341P | missense | gain of function | FGFR2 T341P lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). T341P results in increased phosphorylation of Fgfr2 and is transforming in cell culture (PMID: 9539778). | |
| T370R | missense | unknown | FGFR2 T370R lies within the extracellular domain of the Fgfr2 protein (UniProt.org). T370R has been identified in sequencing studies (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| T370_A371delinsC | indel | unknown | FGFR2 T370_A371delinsC results in a deletion of a threonine (T) and an alanine (A) from aa 370 to aa 371 within the extracellular domain of the Fgfr2 protein, combined with the insertion of a cysteine (C) at the same site (UniProt.org). T370_A371delinsC has been identified in the scientific literature (PMID: 34480077), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Jan 2024). | |
| T370_A371delinsS | indel | unknown | FGFR2 T370_A371delinsS results in a deletion of a threonine (T) and an alanine (A) from aa 370 to aa 371 within the extracellular domain of the Fgfr2 protein, combined with the insertion of a serine (S) at the same site (UniProt.org). T370_A371delinsS has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Jan 2024). | |
| T394A | missense | no effect - predicted | FGFR2 T394A lies within the helical domain of the Fgfr2 protein (UniProt.org). T394A has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 in cultured cells (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| T730S | missense | no effect | FGFR2 T730S (corresponds to T729S in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). T730S has activity similar to wild-type Fgfr2 as demonstrated by equivalent substrate phosphorylation and the lack of oncogenic cell transformation (PMID: 26048680). | |
| T764fs | frameshift | unknown | FGFR2 T764fs results in a change in the amino acid sequence of the Fgfr2 protein beginning at aa 764 of 821, likely resulting in premature truncation of the functional protein (UniProt.org). T764fs has been identified in sequencing studies (PMID: 35280424), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| T786K | missense | unknown | FGFR2 T786K lies within the cytoplasmic domain of the Fgfr2 protein (UniProt.org). T786K has been identified in sequencing studies (PMID: 22960745), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| V248D | missense | unknown | FGFR2 V248D lies within the extracellular domain of the Fgfr2 protein (UniProt.org). V248D is predicted to destabilize the tertiary fold of the Fgfr2 protein based on structural modeling (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| V392A | missense | gain of function - predicted | FGFR2 V392A lies within the transmembrane domain of the Fgfr2 protein (UniProt.org). V392A results in decreased proliferation relative to wild-type Fgfr2 in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| V392M | missense | no effect - predicted | FGFR2 V392M lies within the helical domain of the Fgfr2 protein (UniProt.org). V392M has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Fgfr2 in cultured cells (PMID: 29533785), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| V395D | missense | no effect - predicted | FGFR2 V395D lies within the transmembrane domain of the Fgfr2 protein (UniProt.org). V395D results in proliferation similar to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type in cultured cells (PMID: 34272467), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| V514L | missense | unknown | FGFR2 V514L lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V514L has not been characterized in the scientific literature and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Mar 2024). | |
| V563L | missense | gain of function - predicted | FGFR2 V563L (corresponds to V562L in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V563L is predicted to confer a gain of function to the Fgfr2 protein as indicated by increased Fgfr2 kinase activity in cell culture, and has been shown to be associated with secondary resistance to FGFR inhibitors (PMID: 25169980, PMID: 31109923). | Y |
| V564F | missense | gain of function - predicted | FGFR2 V564F (also referred to as V565F from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V564F results in increased kinase activity in cell culture (PMID: 25169980) and has been shown to be associated with secondary resistance to FGFR inhibitors (PMID: 28034880), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | Y |
| V564I | missense | gain of function | FGFR2 V564I lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V564I confers a gain of function to the Fgfr2 protein as indicated by increased Fgfr2 kinase activity (PMID: 25169980), results in FGF2-independent phosphorylation of Akt and Erk in cell culture (PMID: 29540482), and has been shown to be associated with secondary resistance to FGFR inhibitors (PMID: 25169980). | Y |
| V564L | missense | gain of function - predicted | FGFR2 V564L (also referred to as V565L from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V564L results in increased Fgfr2 kinase activity in cell culture and has been shown to be associated with secondary resistance to FGFR inhibitors (PMID: 25169980), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | Y |
| V564M | missense | unknown | FGFR2 V564M lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V564M has been demonstrated to confer resistance to Fgfr inhibitors in culture (PMID: 25349422), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2023). | Y |
| V564T | missense | no effect - predicted | FGFR2 V564T lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V564T results in activation rates similar to wild-type Fgfr2 in cell culture (PMID: 21454610), and therefore, is predicted to have no effect on Fgfr2 protein function. | |
| V565F | missense | gain of function - predicted | FGFR2 V565F (corresponds to V564F in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V565F results in increased Fgfr2 kinase activity in cell culture (PMID: 25169980) and has been shown to be associated with secondary resistance to FGFR inhibitors (PMID: 28034880, PMID: 31109923), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | Y |
| V565I | missense | gain of function | FGFR2 V565I (corresponds to V564I in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V565I results in increased Fgfr2 kinase activity and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597). | Y |
| V565L | missense | gain of function - predicted | FGFR2 V565L (corresponds to V564L in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V565L has been shown to be associated with secondary resistance to FGFR inhibitors and demonstrates increased Fgfr2 kinase activity in cell culture (PMID: 25169980), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | Y |
| V755I | missense | no effect | FGFR2 V755I (corresponds to V754I in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). V755I has activity similar to wild-type Fgfr2 as demonstrated by equivalent substrate phosphorylation and the lack of oncogenic cell transformation (PMID: 26048680). | |
| V77M | missense | unknown | FGFR2 V77M lies within Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). V77M has been identified in the scientific literature (PMID: 19147536), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| V797* | nonsense | unknown | FGFR2 V797* results in a premature truncation of the Fgfr2 protein at amino acid 797 of 821 (UniProt.org). V797* (corresponding to V702* in a mouse isoform) leads to limited increase in FGFR2 signaling and colony formation in cell culture but promotes tumor formation in a mouse model (PMID: 35948633), and therefore, its effect on Fgfr2 protein function is unknown. | |
| W290* | nonsense | loss of function - predicted | FGFR2 W290* results in a premature truncation of the Fgfr2 protein at amino acid 290 of 821 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), W290* is predicted to lead to a loss of Fgfr2 protein function. | |
| W290C | missense | gain of function | FGFR2 W290C lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). W290C does not result in increased Fgfr2 phosphorylation, but increases both ligand-dependent and ligand-independent dimerization of Fgfr2 (PMID: 23786770), results in a growth advantage relative to wild-type Fgfr2 in a competition assay (PMID: 34272467), is transforming in cell culture (PMID: 23786770, PMID: 34272467), and promotes tumor formation in xenograft models (PMID: 23786770). | |
| W290_I291delinsC | indel | gain of function | 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). | |
| W72C | missense | unknown | FGFR2 W72C lies within Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). W72C has been identified in the scientific literature (PMID: 37541273), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Mar 2024). | |
| wild-type | none | no effect | Wild-type FGFR2 indicates that no mutation has been detected within the FGFR2 gene. | |
| Y281C | missense | unknown | FGFR2 Y281C lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). Y281C has been identified in the scientific literature (PMID: 26003532, PMID: 29104507), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| Y328N | missense | gain of function - predicted | FGFR2 Y328N lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). Y328N results in decreased proliferation in a competition assay but increased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| Y340C | missense | unknown | FGFR2 Y340C lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). Y340C has been identified in sequencing studies (PMID: 16418739), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| Y340H | missense | unknown | FGFR2 Y340H lies within Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). Y340H has been identified in sequencing studies (PMID: 16418739), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| Y375C | missense | gain of function | FGFR2 Y375C lies within the extracellular juxtamembrane domain of the Fgfr2 protein (PMID: 17525745). Y375C results in proliferation similar to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type in cultured cells (PMID: 34272467), but constitutive phosphorylation of Fgfr2 in cell culture, activation of Mapk p38 signaling, and abnormal proliferation and differentiation in the skin and skull of transgenic mouse models (PMID: 22585574). | |
| Y376C | missense | gain of function - predicted | FGFR2 Y376C (corresponds to Y375C in the canonical isoform) lies within the extracellular domain of the Fgfr2 protein (PMID: 17525745). Y376C results in constitutive dimerization through inter-molecular disulfide bonds (PMID: 17525745), and therefore, is predicted to lead to a gain of Fgfr2 protein function. | |
| Y588D | missense | unknown | FGFR2 Y588D lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). Y588D has been identified in sequencing studies (PMID: 25669975), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Dec 2023). | |
| Y769* | nonsense | gain of function - predicted | FGFR2 Y769* results in a premature truncation of the Fgfr2 protein at amino acid 769 of 821 (UniProt.org). Y769* is predicted to lead to a gain of Fgfr2 protein function as a corresponding mouse variant (Y674*) promotes colony formation in cell culture and leads to tumor formation in a mouse model (PMID: 35948633). | |
| Y779C | missense | unknown | FGFR2 Y779C lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). Y779C has been demonstrated to confer resistance to Fgfr inhibitors as a secondary resistance mutation (PMID: 34250419), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Nov 2023). | Y |
| Y812* | nonsense | unknown | FGFR2 Y812* results in a premature truncation of the Fgfr2 protein at amino acid 812 of 821 (UniProt.org). Y812* (corresponding to Y717* in a mouse isoform) leads to limited increase in FGFR2 signaling and colony formation in cell culture but promotes tumor formation in a mouse model (PMID: 35948633), and therefore, its effect on Fgfr2 protein function is unknown. |
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