New oncogenicity classification guidelines for somatic variants

Suggested step-by-step workflow for somatic variant classification and interpretation with this new tool
Evidence strength can be rated Very Strong, Strong, Moderate, or Supporting, and in this case, add up to the different amounts of points
  • Cancer hotspots (OS3, OM4, and OP3): Different from the ACMG guidelines, this standard uses the database cancerhotspots.org as the main resource to determine whether or not the variant lies on a genetic hotspot, with very specific details on the number of samples reported with the same variant needed in order to apply the rule.
  • Previously classified variants in the region (OS1, OM3)
  • In silico prediction tools (OP1, SBP1): Evaluation of bioinformatic predictors is fairly similar to what is described in the ACMG guidelines.
  • Frequency data (OP4, SBVS1, SBS1): The treatment of normal frequency databases is comparable to the one advised in the ACMG germline guidelines, with a slightly reduced contribution to overall oncogenicity.
  • Functional studies (OS2 and SBS2): Similar to the ACMG guidelines, in vitro or in vivo studies have a significant impact on the classification of variants. What’s more, since cancer is a highly prolific field for these types of analysis, it is expected for these rules to be more applicable in comparison to the germline workflow.
  • Etiology (OP2): The standard takes into account the genes that are involved in single-cause malignancies, such as bi-allelic RB1 inactivation in retinoblastoma.

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Franklin by Genoox

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