Standardization of the Interpretation and Reporting of Sequence Variants Identified in Neoplasms

Accurate classification of genetic alterations is important to ensure the provision of high-quality clinical data. For interpretation of germline alterations, there are standardized guidelines dating back to 2000 with the most recent version being a joint publication from the American College of Medical Genetics (ACMG) and the Association of Molecular Pathology (AMP) (Richards et al., 2015, DOI: 10.1038/gim.2015.30). For somatic alterations, guidelines from the Association of Molecular Pathology (AMP), the American Society of Clinical Oncology (ASCO), and the College of American Pathology (CAP) were more recently published to assess and tier variants based on clinical significance (Li et al., 2017, DOI: 10.1016/j.plabm.2020.e00170).

In an effort to enhance the existing guidelines, we developed a formal structured approach for the classification of somatic variants to not only account for a variant's clinical significance but also its ability to drive tumorigenesis. This approach is largely based on the structure of the ACMG/AMP germline guidelines, which has been shown to fit a Bayesian framework (Tavtigian et al., 2018, DOI: 10.1038/gim.2017.210), and adopts elements from both the ACMG/AMP germline guidelines and AMP/ASCO/CAP somatic guidelines.

Join this webinar to learn a method for somatic variant curation.

Learning Objectives:

1. Discuss key elements from the AMP/ASCO/CAP guidelines for somatic variant interpretation and the ACMG/AMP guidelines for germline variant interpretation.

2. Review certain evidence criteria in this newly developed framework and how they may be combined into a classification.

3. Compare the performance of this approach with other classification models.