Neonatal screening is among the most impactful preventative health measures ever implemented. Here, we apply for an investment that will result in an unprecedented expansion of the national screening effort, which has a documented potential to massively prevent mortality and morbidity. The PREDiSPOSED project implements our novel method - Double Batched Sequencing (DoBSeq) - that reduces the cost of identifying rare genetic variants by 94%: saving this project 75M DKK. In combination with the world-leading Danish biobanks and health registries, PREDiSPOSED will conduct nucleotide-resolution genomic screening of 113 genes associated with cancer predisposition syndromes (CPSs) at the lowest cost ever achieved in the world. PREDiSPOSED reports actionable genetic variants back to the participants who can then opt for precision prevention already offered by Danish health care. PREDiSPOSED’s estimated diagnostic output will lead to >7,000 years of life saved, equivalent to >2B DKK in economic impact. Using CPSs as a disease prototype, PREDiSPOSED has five main phases: 1) citizen perception of/response to screening for CPSs, 2) pilot study/testing, 3) retrospective DoBSeq of 200,448 adults (40% are already consented), 4) DoBSeq of 100,376 newborns, and 5) dissemination of results with the expressed aim of permanently expanding/establishing early childhood and adult genomic screening for CPSs and, likely, hundreds of other rare, serious, actionable, genetic conditions.