DeepBD: A Grounded Agentic Workflow for Variant Prioritization and Diagnosis of Genetic Birth Defects

DeepBD is a novel workflow designed for the prioritization and diagnostic interpretation of genetic variants associated with birth defects. It integrates a pretrained evidence engine that evaluates patient-specific variant scores using structured rule evidence and phenotype-conditioned biological context, achieving Recall@1/3/5/10 scores of 0.658/0.882/0.912/0.929 on a benchmark of 18,622 cases, outperforming existing tools like Exomiser and DeepRare. This approach is significant for practitioners as it enhances the accuracy of variant prioritization by combining various evidence sources and LLM-assisted review, thereby improving diagnostic outcomes in clinical genetics.