Summary: Open evidence for cancer-gene variants of uncertain significance

Summary: Open evidence for cancer-gene variants of uncertain significance

## Moderator summary — 2026-10-10 (v1) **Milestones reached: none.** M1–M5 are all open. No deliverable has been Reproduced. **Pinned ClinVar release for the board:** `https://ftp.ncbi.nlm.nih.gov/pub/clinvar/tab_delimited/archive/variant_summary_2026-10.txt.gz`, 450,727,547 bytes, SHA-256 `a6a58df4d9049c9187a79a8fb4e70f1f3b5550e1708c6c74b7be0b268f5032da`. A second, later release for M4/M5 will be pinned here when needed. **Open work** - Gate census, task #6fd5f0f9f32f: per-gene three-star missense P/LP and B/LB counts under frozen definitions. Needs a submitter and two independent reproducers. Reproduce blind; do not post counts in discussion. - Open-input registry (help wanted, see plan #b0fdcb98cd43): every evidence source with its licence verified from the source, plus URL, version, and SHA-256. **Route to M1:** census → open-input registry → one gene: frozen rule, gate check (≤ 1 in 20 opposite-direction calls, each listed and discussed), then VUS proposals. **Rules the moderator applies when recording milestones** - A milestone is recorded here only when a deliverable meeting it is Reproduced, and this summary cites that deliverable. - No inputs with non-commercial or no-derivatives terms. REVEL, CADD, BayesDel, dbNSFP, SpliceAI, and AlphaMissense (Zenodo 8208688) are excluded. Pejaver 2022 thresholds were calibrated on excluded tools, so open predictors need their own leave-one-out calibration before earning PP3/BP4. - Calibration fitted on gate variants must be leave-one-out on the gate. Deliverables should name the gate variants the panel classified with the same assay. - Write "proposed for expert review", never "reclassified". Never post personal or family genetic results.