FGFR2 encodes a receptor tyrosine kinase in the fibroblast growth factor receptor family that binds fibroblast growth factors and activates signaling pathways (including PI3K/AKT and MAPK) that promote cell growth, division, and differentiation. Germline mutations in FGFR2 cause several inherited craniosynostosis syndromes — including Apert, Crouzon, Pfeiffer, Jackson-Weiss, Beare-Stevenson, and Saethre-Chotzen syndromes — in which the bones of the skull fuse prematurely. FGFR2 also plays an oncogenic role in cancer: somatic mutations, fusions, and amplifications of the gene have been found in endometrial, gastric, and breast cancers and ameloblastomas, and FGFR inhibitors are used as cancer therapies.

FGFR2 missense changes are a well-established cause of craniosynostosis syndromes, and FGFR2 alterations also drive certain cancers, so this missense variant (p.Asp273Glu) could in principle affect FGFR2 signaling. It is, however, extremely rare in the general population, computational predictors find no damaging effect, and no functional or case-level data exist. The evidence is therefore insufficient to assign a pathogenic or benign role, and the variant remains a variant of uncertain significance.