Clinical significance annotation for Non-coding and Fusion variants
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17 months ago
bt_cepo ▴ 40

Hi everyone!

I am fine tuning a pipeline for the annotation of DNA variants in cancer patients. Until this moment, I have been using the CMC tier provided By COSMIC (https://cancer.sanger.ac.uk/cmc/home#:~:text=The%20Cancer%20Mutation%20Census%20(CMC,driving%20different%20types%20of%20cancer.).

It ranks mutations according to their documented pathogenicity and has served me to sort variants based on their clinical significance. However, it only accounts for coding variants.

I am struggling to find classifications that provide a ranking for non-coding and gene fusion variants. Are there any resoruces of this kind for these variants? Are they not really relevant when assessing the clinical impact in cancer?

Might be a too broad question but would appreciate any starting point.

Thanks!!

variant-annotation • 457 views
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this is more or less open ocean.

tools exist, yes, but generating a rank ordered list of pathogenicity for a list of such variants is at present subject to incomplete biological understanding (e.g., regarding key aspects of gene regulatory models for non coding, or protein dynamics for fusions), lack of available, comprehensive data sources such as would be needed to train an AI model, etc.

for tools, I'd go to pubmed and look for reviews on "pathogenicity of non coding variants" or what have you.

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