In developed countries, Newborn Screening (NBS) programs aim to detect treatable yet clinically silent disorders. The selection of disorders to be included in NBS considers severity, treatment availability, prevalence, and analysis cost. However, numerous genetic disorders remain excluded from routine testing due to high expenses and specialized equipment requirements. Here we present SCAN, a novel, non-invasive, and cost-effective decision-support tool utilizing nanopore sequencing for estimating proportions of chromosomes responsible for the most common aneuploidies. SCAN combines DNA enrichment (amplification), barcoding, nanopore sequencing, and machine learning predictive modeling. In a proof-of-concept study for Klinefelter Syndrome, SCAN achieved 100% sensitivity, specificity, and accuracy, becoming the world’s first IVD-certified genetic test utilising nanopore sequencing. Further model training shows promise in expanding this assay to detect other chromosomal aneuploidies included in the protocol.