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griffithlab / civic-v2

CIViC is an open access, open source, community-driven web resource for Clinical Interpretation of Variants in Cancer
https://civicdb.org
MIT License
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Oncogenicity Assertions in CIViC V2 #538

Closed arpaddanos closed 2 years ago

arpaddanos commented 2 years ago

Related issue 537 on Oncogenic/Pathogenic EID rework

Using the model set by Predisposing Assertions, we will create an Oncogenicity Assertion. The Assertion will collect Oncogenic and Functional EIDs, as well as other types, to create an evaluation of variant Oncogenicity (conceptualized as variant ability to drive processes associated with Hallmarks of Cancer as defined by Hannahan and Weinberg). The Assertion will also leverage the recently published Standards for the classification of pathogenicity of somatic variants in cancer (oncogenicity): Joint recommendations of Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC), and Variant Interpretation for Cancer Consortium (VICC) for systematic assessment.

Screen Shot 2022-05-27 at 2 21 45 AM

A scale and codes are used to evaluate variant benign/oncogenic annotation.

Screen Shot 2022-05-27 at 2 22 06 AM

Among the most important unresolved issues for this Assertion are:

Screen Shot 2022-05-27 at 2 21 55 AM
arpaddanos commented 2 years ago

Important note on the parallel development of Oncogenic EIDs (See Issue 537) and Oncogenic Assertions. The proposed Clinical Significance for Oncogenic EIDs will not be reflected in the first iteration of the CIViC Oncogenicity Assertion, as there are no published guidelines for the Protective axis of the the Disease Causality scale. Figure below summarizes this.

Screen Shot 2022-05-27 at 2 59 02 AM

Note that the ides in this figure also apply to the new proposed model for Predisposing EIDs in relation to the Predisposing AID

arpaddanos commented 2 years ago

Note that if Oncogenicity codes are added to Oncogenic EIDs, then a corresponding addition of ACMG codes to Predisposing EIDs should be considered.

arpaddanos commented 2 years ago

Would SC-VCEP codes be built into the Oncgenic AID? Or should these SC-VCEP specific guidelines be part of a structured way of writing the AID Statement?

kkrysiak commented 2 years ago

Assertion Oncogenicity codes should consider new rules being used for NTRK fusions. Basically, in addition to the oncogenicity codes for snvs/indels, we should consider support for new fusion rules in development (this may be a future direction).

arpaddanos commented 2 years ago

That's right @kkrysiak. It is something we should do and also I agree it is a future direction. It should be implemented once the NTRK SC-VCEP has published its guidelines, since I think that is part of the roadmap.

malachig commented 2 years ago

https://lucid.app/lucidspark/23ae4dc2-a014-4e02-b259-366208a47407/edit?viewport_loc=-1426%2C-769%2C5376%2C2928%2C0_0&invitationId=inv_8a4a7a13-a05a-4608-a4ff-fef0890aa56f#