 Hi, I'm Alexandra Martins. I'm a researcher from the French Institute of Health and Medical Research, known as INSERM. We are here at the research unit U1079, which is hosted by the Faculty of Medicine of the University of Rouen in France. Our unit focuses on the genetics of cancer and neuropsychiatric disorders. It relies on close interactions between biologists and clinicians, including geneticists and pathologists from the University Hospital, which is just across the street. I'm here today to give you a highlight of our article recently published in the journal Human Mutation. Functional analysis of a large set of BRCA2X7 variants highlights the predictive value of eczema scores in detecting alterations of eczemic, splicing regulatory elements. As you know, with next-generation sequencing, the main challenge in medical genetics is no longer the identification of genetic variants, but their interpretation. This is particularly important in hereditary disorders, such as hereditary breast and ovarian cancer, a syndrome that most frequently results from germline mutations in the BRCA1 and BRCA2 genes. The identification of the causal mutation is essential for diagnosis, patient follow-up and genetic counseling. However, the number of variants of a known significance is very high, while some of these variants may be deleterious, for instances, by affecting RNA-splicing signals. RNA-splicing not only requires particular sequences at the axon-intron boundaries, which define the spliced sites, but is also dependent on splicing regulatory elements, such as eczemic splicing enhancers and axon-splicing silencers. Presently, it is very difficult to assess which genetic variants alter this type of regulatory signals. Splicing regulatory elements are still poorly known and are difficult to predict using currently available in silico tools. Another difficulty is that patient's RNA is often unavailable for analysis. To circumvent these limitations, we developed minigine assays that help identify splicing mutations. Briefly, we first prepare splicing-competent minigines carrying the variants of interest, and then, after transfection into human cells, the splicing pattern of the mutant minigines is compared to that of the wild type by performing RT-PCR analysis. Recently, we used this approach to evaluate the impact on splicing of all variants identified in the axon-7 of BRCA2. Our results now published in Human Mutation revealed an unexpected high number of splicing mutations in this axon. We also found that most of these mutations increased axon skipping by altering potential splicing regulatory elements. We then exploited this large set of splicing data to test the predictive value of splicing regulator sequence scores recently established by the Chassin Laboratory. We were happy to find that this new approach could discriminate quite well between mutations that induced BRCA2 axon skipping from those that did not. Thus, our data suggests that this new in silico approach represents a promising tool to prioritize axonic variants for functional assays. I'd like to thank all the people involved in this project. If you'd like to learn more about this work, we invite you to read our article in Human Mutation. And also, if you have comments or questions, please send me an email. Thanks for your attention.