DNMT3A R635W Mutation in OCIAML2 annotation inconsistency

Issues and Bugs
1

Hi,

I noticed annotation inconsistency of the DNMT3A R635W mutation in OCIAML2. If I search for OCIAML2 cell line in the DepMap portal, DNMT3A R635W is annotated as “likely oncogenic” and “likely loss-of-function” in the “Oncogenic Alterations” section of the page. However, in the downloaded OmicsSomaticMutations.csv file for 23Q2, this mutation is not annotated as “LikelyLoF” or “CCLEDeleterious”, or “AssociatedWith” “gene_function_loss;”. And in the custom download file for DNMT3A with “Damaging Mutations”, OCIAML2 is not included. I’m not sure where what caused this inconsistency. However, since this mutation is known to be a likely LOF mutation (OncoKB™ - MSK's Precision Oncology Knowledge Base, Gene Variant Detail), I hope you can look into this issue. Thanks!

2

Hi,

Thanks for reaching out. As of 23Q2, the LoF annotation in our mutation data did not take OncoKB into account, and was independent of the Oncogenic Alterations tab in the portal, which is why there were some discrepancies. We addressed this problem in the upcoming 23Q4 release by incorporating OncoKB (and other additional annotators) in our mutation pipeline to improve our functional annotation. Please stay tuned!

Simone

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