Homozygous FANCM variant c.5101C>T p.(Gln1701*) in a patient with early onset breast cancer, chemotherapy toxicity, and chromosome fragility

not-yet-known not-yet-known not-yet-known unknown Background Biallelic FANCM variants are linked to a Fanconi anemia-like cancer predisposition syndrome which includes early onset breast cancer, chemotherapy toxicity and chromosome fragility. Additionally, heterozygous truncating variants have been linked to increased breast cancer risk. However, the published results have been inconsistent, and the risks and the functional effects associated with the variants also vary depending on the position in the gene, with N-terminal truncating variants having a stronger effect. Compared to other FANCM variants studied, milder patient phenotypes and only late onset breast cancer have been reported for the homozygous C-terminal c.5101C>T variant, which is enriched in Finland. Case We report here a Finnish patient, homozygous for the FANCM c.5101C>T, p.(Gln1701*) variant, who manifested with early onset triple negative breast cancer, chemotherapy toxicity and chromosome fragility. The homozygous c.5101C>T has previously been reported in two Finnish siblings with primary ovarian insufficiency and chromosome fragility. Conclusion These findings suggest that the C-terminal FANCM variant c. 5101C>T may also cause a phenotype similar to the phenotype caused by N-terminal truncating variants, when inherited in a homozygous state.