Modeling the ACMG/AMP variant classification guidelines as a Bayesian classification framework

We evaluated the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) variant pathogenicity guidelines for internal consistency and compatibility with Bayesian statistical reasoning.The ACMG/AMP criteria were translated into a naive Bayesian classifier, assuming four levels of evidence and exponentially scaled odds of pathogenicity. We tested this framework with a range of prior probabilities and odds...