About this webinar

Recorded On: Wednesday, June 10, 2020

Before assessing the clinical significance of a somatic mutation, one must determine if the mutation is likely to be a driver mutation (i.e. a mutation that provides a selective growth advantage, thereby promoting cancer development). To aid clinicians in this process, VSClinical provides an oncogenicity scoring system, which uses a variety of metrics to classify a given somatic mutation into one of the following categories: oncogenic, likely oncogenic, benign, likely benign, or uncertain significance. This scoring system is heavily inspired by the ACMG Guidelines for the interpretation of germline mutations but has several important differences to make it more applicable in the context of somatic variant interpretation.

Our oncogenicity scoring system relies on an additive point system in which points are assigned to a given variant based on several criteria. The various criteria that are considered when evaluating a given variant are summarized on the table below:

Many of the criteria above are shared by the ACMG Guidelines for germline variant interpretation, such as population frequency information, variant effect on protein function, and nearby pathogenic variants in catalogs such as ClinVar. However, other criteria are specific to the world of somatic variant interpretation. These include the variant’s presence in somatic catalogs, the effect of other known oncogenic variants in the same gene, and the variant’s presence in known cancer hotspots or active binding sites.  These criteria are combined by summing over the scores for all applicable scoring criteria. Scores exceeding 3 indicate an oncogenic or likely oncogenic classification, while scores falling below -3 indicate a benign or likely benign classification.

In our upcoming webcast, I will discuss how each of these scoring criteria are combined to obtain an oncogenicity classification. This will include a discussion of the considerations taken into account during the development of this scoring system and a detailed analysis of several example mutations to illustrate the system in practice.