Germline protein truncating variants (PTVs) in the FANCM gene have been associated with a 2-4-fold increased breast cancer risk in case-control studies conducted in different European populations. However, the distribution and the frequency of FANCM PTVs in Europe have never been investigated. In the present study, we collected the data of 114 European female breast cancer cases with FANCM PTVs ascertained in 20 centers from 13 European countries. We identified 27 different FANCM PTVs. The p.Gln1701* PTV is the most common PTV in Northern Europe with a maximum frequency in Finland and a lower relative frequency in Southern Europe. On the contrary, p.Arg1931* seems to be the most common PTV in Southern Europe. We also showed that p.Arg658*, the third most common PTV, is more frequent in Central Europe, and p.Gln498Thrfs*7 is probably a founder variant from Lithuania. Of the 23 rare or unique FANCM PTVs, 15 have not been previously reported. We provide here the initial spectrum of FANCM PTVs in European breast cancer cases.

Àrea of Molecular and Clinical Genetics University Hospital Vall d´Hebron Barcelona 08035 Spain

Biomedical Sciences Institute University of Porto Porto 4050 313 Portugal

Biosciences Laboratory Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS Meldola 47014 Italy

Center for Genomic Medicine Copenhagen University Hospital Rigshospitalet Copenhagen 2100 Denmark

Centre for Medical Genetics and Reproductive Medicine Gennet Prague 17000 Czech Republic

Centro de Investigación en Red de Enfermedades Raras Madrid 28029 Spain

Department of Clinical Genetics Karolinska University Hospital and Department of Molecular Medicine Karolinska Institutet Stockholm 17176 Sweden

Department of Clinical Pathology The University of Melbourne Melbourne 3010 Australia

Department of Experimental and Clinical Biomedical Sciences University of Florence Florence 50134 Italy

Department of experimental preventive and clinical medicine State Research Institute Centre for Innovative Medicine Vilnius 08410 Lithuania

Department of Genetics Portuguese Oncology Institute of Porto Porto 4200 072 Portugal

Department of Gynaecology Center of Obsterics and Gynaecology Vilnius University Hospital Santaros Klinikos Vilnius 08410 Lithuania

Department of Histopathology and Cytology Clinical Hospital Acibadem Sistina Skopje 1000 Republic of North Macedonia

Department of Medical Genetics GHC Genetics Prague 11000 Czech Republic

Department of Medical Oncology and Hematology Unit of Medical GeneticsFondazione IRCCS Istituto Nazionale dei Tumori Milan 20133 Italy

Department of Medical Oncology University Hospital Vall d´Hebron Barcelona 08035 Spain

Department of Molecular Genetics National Institute of Oncology Budapest 1122 Hungary

Department of Obstetrics and Gynecology Helsinki University Hospital and University of Helsinki HUS Helsinki 00029 Finland

Department of Research Unit of Molecular Bases of Genetic Risk and Genetic Testing Fondazione IRCCS Istituto Nazionale dei Tumori Milan 20133 Italy

Division of Cancer Prevention and Genetics IEO European Institute of Oncology IRCCS Milan 20141 Italy

Division of Clinical Genetics Department of Laboratory Medicine Lund University Lund SE 22100 Sweden

Division of Oncology and Pathology Department of Clinical Sciences Lund Lund University Lund SE 22381 Sweden

Familial Cancer Clinical Unit Human Cancer Genetics Programme Spanish National Cancer Research Centre Madrid 28029 Spain

Fundación Pública Galega Medicina Xenómica SERGAS Santiago de Compostela 15706 Spain

Genetics Department F76000 and Normandy University UNIROUEN Inserm U1245 Normandy Centre for Genomic and Personalized Medicine Rouen University Hospital Rouen France

Genome Diagnostics Program IFOM the FIRC Institute for Molecular Oncology Milan 20139 Italy

Genotyping Unit CEGEN Human Cancer Genetics Programme Spanish National Cancer Research Centre Madrid 28029 Spain

Hereditary Cancer Center Hematology Oncology and Transfusion Medicine Center Vilnius University Hospital Santaros Klinikos Vilnius 08410 Lithuania

Hereditary Cancer Group Vall d'Hebron Institute of Oncology Barcelona 08035 Spain

Hereditary Cancer Program Catalan Institute of Oncology ONCOBELL IDIBELL IDIBGI IGTP CIBERONC Barcelona 08908 Spain

Human Genetics Group Human Cancer Genetics Programme Spanish National Cancer Research Centre Madrid 28029 Spain

InRASTES Molecular Diagnostics Laboratory National Centre for Scientific Research Demokritos Athens 15310 Greece

Inserm U900 Institut Curie PSL University Paris F 75005 France

Institute of Biochemistry and Experimental Oncology 1st Faculty of Medicine Charles University Prague 12853 Czech Republic

Institute of Biology and Medical Genetics General University Hospital and 1st Faculty of Medicine Charles University Prague 12800 Czech Republic

Institute of Medical Sciences University of Rzeszow Rzeszow 35 310 Poland

Instituto de Investigación Sanitaria de Santiago de Compostela Santiago de Compostela 15706 Spain

Medical Faculty University Clinic of Radiotherapy and Oncology Ss Cyril and Methodius University in Skopje Skopje 1000 Republic of North Macedonia

Mines ParisTech Fontainebleau F 77300 France

National Center of Pathology Vilnius University Hospital Santaros Klinikos Vilnius 08410 Lithuania

Office for Medical Services Region Skåne Department of Clinical Genetics and Pathology Laboratory Medicine Lund SE 22100 Sweden

Precision Medicine School of Clinical Sciences at Monash Health Monash University Clayton 3168 Australia

Research Centre for Genetic Engineering and Biotechnology 'Georgi D Efremov' Macedonian Academy of Sciences and Arts Skopje 1000 Republic of North Macedonia

Service de Génétique Institut Curie Inserm U830 Paris Descartes University Paris F 75005 France

Spanish Network on Rare Diseases Madrid 28029 Spain

University Modena Hospital Modena 41124 Italy

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