P633: Benchmarking variant classification quality: Concordance of an ACMG-based framework with >400,000 ClinVar submissions from over a decade of clinical testing

Accurate genomic variant classification is foundational to clinical interpretation and patient care. Although the American College of Medical Genetics and Genomics and Association of Molecular Pathology (ACMG/AMP) guidelines offer a standardized scaffold for evaluating evidence and assigning pathogenicity, their application requires nuanced judgment, continuous quality oversight, and standardization protocols for implementation. Variant classification at our laboratory is a semi-automated process informed by an ACMG/AMP-based framework, utilizing information from public resources and internal databases, machine-learning algorithms, and in-depth evaluation by a large team of skilled professionals.