SOP and evidence codes for somatic variant oncogenicity/clinical actionability

[malachig]

Selected for morning session lead by Arpad and Dmitry. Proposal to build support for somatic evidence into the ACMG evidence codes.

[ahwagner]

Marilyn Li notes that common practice is to use somatic evidence in the interpretation of a germline variant, and vice-versa.

[ahwagner]

The group discussed the need for citing use of specific resources in a standard. Agreed that there is a need for a specific workflow in standards, but that evolving practice changes what those workflows look like. Thus, we need to arrive at a solution that provides both specificity and flexibility for evolving practices.

[malachig]

We reviewed proposed oncogenicity codes, discussed specific examples, worked through some of the challenges to the idea that implementing somatic interpretation codes could be done by a relatively minor update to the ACMG codes and could mimic the spirit of ACMG guidelines almost exactly. Some points of debate:

• Interpreting somatic evidence for germline variant interpretation has subtle but important differences to using germline evidence to interpret somatic variants
• Hotspot evidence for somatic variants. What is makes a hotspot a hotspot? What hotspot resource is best? Why not 3D hotspots?
• ...

[malachig]

Proposal to use two genes, TP53 and PTEN as a proof-of-principle experiment for a combined germline and somatic variant interpretation guideline scheme that is based on the ACMG germline guidelines but incorporates fundamental somatic evidence concepts.

[arpaddanos]

PostV1.pdf

[arpaddanos]

ASHG poster PostV1.pdf summarizes the main ideas from this session as well as a model for how CIViC can adapt oncogenicity codes utilizing the proposed new Biological Evidence Item as well as Biological Assertion based on Oncogenicity Codes.