The BReast CAncer genes 1 (BRCA1) and 2 (BRCA2) are the best known genes associated with a highly increased breast cancer risk. Genes like ATM and BARD1 are associated with a moderately increased risk. All of these are involved in the repair of DNA double strand breaks (DSB) by homologous recombination (HR). With the implementation of next generation sequencing technologies in routine molecular diagnostics, the number of variants detected increases steeply. Determining the functional effect for missense variants is challenging, and these are often classified as 'variants of unknown clinical significance' (VUS). Such VUS complicate risk counseling, assessment and treatment of cancer patients. There is a high need for reliable functional assays, which introduce the protein containing the variant in a system to test its effectiveness.