Evidence claim
Evidence summary: somatic small-variant oncogenicity
Summary of Assess somatic small-variant oncogenicity
Two predictor comparisons join the existing OncoVI evidence; their values cannot be pooled. In Chen et al. 2020 (peer reviewed), 33 predictors scored somatic missense mutations labelled by OncoKB curation or by the authors' own cell viability assays, with likely neutral or assay-neutral somatic negatives. The authors co-developed one scored tool, CanDrA, and developed none of the others. With each tool's own default calls, the highest accuracy was 0.70 on OncoKB labels (DEOGEN2, sensitivity 0.87, specificity 0.51), and several tools called most neutral mutations damaging, for example M-CAP with sensitivity 0.97 and specificity 0.11, and CanDrA with specificity 0.17 and the lowest accuracy, 0.49. On the assay labels the highest default accuracy was 0.65 (PrimateAI). When each tool's median score on the test draw was used as the threshold, which ranks tools but is not an operating point a reviewer could apply, the highest accuracy was 0.69 on OncoKB labels (PROVEAN and VEST4) and 0.70 on assay labels (CTAT-cancer and PrimateAI), and FATHMM-disease scored 0.50 on OncoKB labels. Chen et al. print each value as a mean with a range of two standard deviations over 100 draws, not a confidence interval, and do not say which OncoKB positive set fed these tables. In a single-author bioRxiv preprint that is not peer reviewed (Lee 2026), 49 scores were compared on Cancer Gene Census missense variants whose negatives are germline-benign labels (ClinVar benign or likely benign, and gnomAD common variants), which this use case does not accept as somatic controls. In that table 42 of the 49 scores had a lower AUROC on oncogene variants than on tumour-suppressor variants, for example AlphaMissense 0.885 against 0.900 and CADD 0.821 against 0.894, while popEVE went the other way (0.900 against 0.842). The highest all-gene AUROC was 0.876 (MutScore); these AUROC values are rounded here to three decimals from the table's full precision. None of these comparisons covers small indels, calibrated probabilities, criterion-level evidence strength, drug response or reviewer agreement.
Plain-language summary of what the reviewed evidence shows. Draft until reviewed.
Evidence
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Evidence table
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49 evidence rows matching the loaded filters
| Property and statement | Original source and location | Review and provenance |
|---|---|---|
| Claimed field summary Context-only references | Comprehensive assessment of computational algorithms in predicting cancer driver mutations somatic-oncogenicity-20261009-source-chen2020-additional-file-9 and -10: Benchmark 2; somatic-oncogenicity-20261009-source-chen2020-additional-file-21 and -22: Benchmark 5; somatic-oncogenicity-20261009-source-chen2020: Methods and reference 7; somatic-oncogenicity-20261009-source-lee2026-oncocal-tool-performance: tables/tool_performance.tsv; somatic-oncogenicity-20261009-source-lee2026: Methods and Results Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Genome Biology 21:43, published 2020-02-20; PMC7033911 full-text XML | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record |
| Claimed field summary Context-only references | Chen et al. 2020, Additional file 10: Performance metrics of 17 algorithms, default categories, benchmark 2 (OncoKB) somatic-oncogenicity-20261009-source-chen2020-additional-file-9 and -10: Benchmark 2; somatic-oncogenicity-20261009-source-chen2020-additional-file-21 and -22: Benchmark 5; somatic-oncogenicity-20261009-source-chen2020: Methods and reference 7; somatic-oncogenicity-20261009-source-lee2026-oncocal-tool-performance: tables/tool_performance.tsv; somatic-oncogenicity-20261009-source-lee2026: Methods and Results Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: 13059_2020_1954_MOESM10_ESM.xlsx | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record |
| Claimed field summary Context-only references | Chen et al. 2020, Additional file 21: Performance metrics of 33 algorithms, median-score threshold, benchmark 5 (cell viability) somatic-oncogenicity-20261009-source-chen2020-additional-file-9 and -10: Benchmark 2; somatic-oncogenicity-20261009-source-chen2020-additional-file-21 and -22: Benchmark 5; somatic-oncogenicity-20261009-source-chen2020: Methods and reference 7; somatic-oncogenicity-20261009-source-lee2026-oncocal-tool-performance: tables/tool_performance.tsv; somatic-oncogenicity-20261009-source-lee2026: Methods and Results Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: 13059_2020_1954_MOESM21_ESM.xlsx | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record |
| Claimed field summary Context-only references | Chen et al. 2020, Additional file 22: Performance metrics of 17 algorithms, default categories, benchmark 5 (cell viability) somatic-oncogenicity-20261009-source-chen2020-additional-file-9 and -10: Benchmark 2; somatic-oncogenicity-20261009-source-chen2020-additional-file-21 and -22: Benchmark 5; somatic-oncogenicity-20261009-source-chen2020: Methods and reference 7; somatic-oncogenicity-20261009-source-lee2026-oncocal-tool-performance: tables/tool_performance.tsv; somatic-oncogenicity-20261009-source-lee2026: Methods and Results Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: 13059_2020_1954_MOESM22_ESM.xlsx | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record |
| Claimed field summary Context-only references | Chen et al. 2020, Additional file 9: Performance metrics of 33 algorithms, median-score threshold, benchmark 2 (OncoKB) somatic-oncogenicity-20261009-source-chen2020-additional-file-9 and -10: Benchmark 2; somatic-oncogenicity-20261009-source-chen2020-additional-file-21 and -22: Benchmark 5; somatic-oncogenicity-20261009-source-chen2020: Methods and reference 7; somatic-oncogenicity-20261009-source-lee2026-oncocal-tool-performance: tables/tool_performance.tsv; somatic-oncogenicity-20261009-source-lee2026: Methods and Results Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: 13059_2020_1954_MOESM9_ESM.xlsx | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record |
| Claimed field summary Context-only references | An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers somatic-oncogenicity-20261009-source-chen2020-additional-file-9 and -10: Benchmark 2; somatic-oncogenicity-20261009-source-chen2020-additional-file-21 and -22: Benchmark 5; somatic-oncogenicity-20261009-source-chen2020: Methods and reference 7; somatic-oncogenicity-20261009-source-lee2026-oncocal-tool-performance: tables/tool_performance.tsv; somatic-oncogenicity-20261009-source-lee2026: Methods and Results Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: bioRxiv 2026.07.16.739080 v1, posted 2026-07-23; full-text HTML page | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: SHA-256 of one retrieval of the full-text HTML page, which is mutable (site chrome, metrics). The PDF request returned HTTP 429. |
| Claimed field summary Context-only references | OncoCal repository, tables/tool_performance.tsv (per-tool AUROC and AUPRC by gene role) somatic-oncogenicity-20261009-source-chen2020-additional-file-9 and -10: Benchmark 2; somatic-oncogenicity-20261009-source-chen2020-additional-file-21 and -22: Benchmark 5; somatic-oncogenicity-20261009-source-chen2020: Methods and reference 7; somatic-oncogenicity-20261009-source-lee2026-oncocal-tool-performance: tables/tool_performance.tsv; somatic-oncogenicity-20261009-source-lee2026: Methods and Results Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: commit 40b7770f2a768ba800c4f4c6b48e2bfe967ed14a (2026-07-11) | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record |
Pinned records1081 values
| Comprehensive assessment of computational algorithms in predicting cancer driver mutations somatic-oncogenicity-20261009-source-chen2020-additional-file-9 and -10: Benchmark 2; somatic-oncogenicity-20261009-source-chen2020-additional-file-21 and -22: Benchmark 5; somatic-oncogenicity-20261009-source-chen2020: Methods and reference 7; somatic-oncogenicity-20261009-source-lee2026-oncocal-tool-performance: tables/tool_performance.tsv; somatic-oncogenicity-20261009-source-lee2026: Methods and Results Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Genome Biology 21:43, published 2020-02-20; PMC7033911 full-text XML | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record |
Pinned records1081 values
| Chen et al. 2020, Additional file 10: Performance metrics of 17 algorithms, default categories, benchmark 2 (OncoKB) somatic-oncogenicity-20261009-source-chen2020-additional-file-9 and -10: Benchmark 2; somatic-oncogenicity-20261009-source-chen2020-additional-file-21 and -22: Benchmark 5; somatic-oncogenicity-20261009-source-chen2020: Methods and reference 7; somatic-oncogenicity-20261009-source-lee2026-oncocal-tool-performance: tables/tool_performance.tsv; somatic-oncogenicity-20261009-source-lee2026: Methods and Results Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: 13059_2020_1954_MOESM10_ESM.xlsx | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record |
Pinned records1081 values
| Chen et al. 2020, Additional file 21: Performance metrics of 33 algorithms, median-score threshold, benchmark 5 (cell viability) somatic-oncogenicity-20261009-source-chen2020-additional-file-9 and -10: Benchmark 2; somatic-oncogenicity-20261009-source-chen2020-additional-file-21 and -22: Benchmark 5; somatic-oncogenicity-20261009-source-chen2020: Methods and reference 7; somatic-oncogenicity-20261009-source-lee2026-oncocal-tool-performance: tables/tool_performance.tsv; somatic-oncogenicity-20261009-source-lee2026: Methods and Results Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: 13059_2020_1954_MOESM21_ESM.xlsx | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record |
Sources and history
Release 2026-11-02-a7f03c9e55a5 · Record review: source checked
7 source records and release history
- Comprehensive assessment of computational algorithms in predicting cancer driver mutations · Original source · Genome Biology 21:43, published 2020-02-20; PMC7033911 full-text XML
- Chen et al. 2020, Additional file 9: Performance metrics of 33 algorithms, median-score threshold, benchmark 2 (OncoKB) · Original source · 13059_2020_1954_MOESM9_ESM.xlsx
- Chen et al. 2020, Additional file 10: Performance metrics of 17 algorithms, default categories, benchmark 2 (OncoKB) · Original source · 13059_2020_1954_MOESM10_ESM.xlsx
- Chen et al. 2020, Additional file 21: Performance metrics of 33 algorithms, median-score threshold, benchmark 5 (cell viability) · Original source · 13059_2020_1954_MOESM21_ESM.xlsx
- Chen et al. 2020, Additional file 22: Performance metrics of 17 algorithms, default categories, benchmark 5 (cell viability) · Original source · 13059_2020_1954_MOESM22_ESM.xlsx
- An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers · Original source · bioRxiv 2026.07.16.739080 v1, posted 2026-07-23; full-text HTML page
- OncoCal repository, tables/tool_performance.tsv (per-tool AUROC and AUPRC by gene role) · Original source · commit 40b7770f2a768ba800c4f4c6b48e2bfe967ed14a (2026-07-11)
Technical metadata and extraction receipts
Stable ID: use-case-summary-somatic-small-variant-oncogenicity
- field
- summary
- value
- Two predictor comparisons join the existing OncoVI evidence; their values cannot be pooled. In Chen et al. 2020 (peer reviewed), 33 predictors scored somatic missense mutations labelled by OncoKB curation or by the authors' own cell viability assays, with likely neutral or assay-neutral somatic negatives. The authors co-developed one scored tool, CanDrA, and developed none of the others. With each tool's own default calls, the highest accuracy was 0.70 on OncoKB labels (DEOGEN2, sensitivity 0.87, specificity 0.51), and several tools called most neutral mutations damaging, for example M-CAP with sensitivity 0.97 and specificity 0.11, and CanDrA with specificity 0.17 and the lowest accuracy, 0.49. On the assay labels the highest default accuracy was 0.65 (PrimateAI). When each tool's median score on the test draw was used as the threshold, which ranks tools but is not an operating point a reviewer could apply, the highest accuracy was 0.69 on OncoKB labels (PROVEAN and VEST4) and 0.70 on assay labels (CTAT-cancer and PrimateAI), and FATHMM-disease scored 0.50 on OncoKB labels. Chen et al. print each value as a mean with a range of two standard deviations over 100 draws, not a confidence interval, and do not say which OncoKB positive set fed these tables. In a single-author bioRxiv preprint that is not peer reviewed (Lee 2026), 49 scores were compared on Cancer Gene Census missense variants whose negatives are germline-benign labels (ClinVar benign or likely benign, and gnomAD common variants), which this use case does not accept as somatic controls. In that table 42 of the 49 scores had a lower AUROC on oncogene variants than on tumour-suppressor variants, for example AlphaMissense 0.885 against 0.900 and CADD 0.821 against 0.894, while popEVE went the other way (0.900 against 0.842). The highest all-gene AUROC was 0.876 (MutScore); these AUROC values are rounded here to three decimals from the table's full precision. None of these comparisons covers small indels, calibrated probabilities, criterion-level evidence strength, drug response or reviewer agreement.
- source locator
- somatic-oncogenicity-20261009-source-chen2020-additional-file-9 and -10: Benchmark 2; somatic-oncogenicity-20261009-source-chen2020-additional-file-21 and -22: Benchmark 5; somatic-oncogenicity-20261009-source-chen2020: Methods and reference 7; somatic-oncogenicity-20261009-source-lee2026-oncocal-tool-performance: tables/tool_performance.tsv; somatic-oncogenicity-20261009-source-lee2026: Methods and Results
- review
- method: source-hash-verification; independent-cell-check; automated-source-review; reviewer: claude; reviewer note: Separate Claude review agent, independent of the collector who drafted the summary proposal; the reviewer corrected the text; no human review claimed; reviewed at: 2026-10-09T21:06:32Z; note: Drafted by the collector in coverage.json summary_proposal and corrected by the reviewer; every number traced to stored source_checked results. Descriptive summary only; no execution, human scientific review or clinical validation. See docs/reviews/use-cases/somatic-small-variant-oncogenicity-2026-10-09.md.
- pins
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