The germline DNA repair gene landscape in <i>BRCA1</i> and <i>BRCA2</i> implicated hereditary breast cancer families
Bibliographic record
Abstract
ABSTRACT As gene-panels expand to include candidate breast cancer predisposing genes (CPGs) involved in diverse DNA repair pathways, we investigated an index breast cancer (BC) case from 56 BRCA1 or BRCA2 implicated high-risk hereditary BC families for rare germline variants predicted to be damaging and clinically relevant in 276 DNA repair genes (DRGs). Using whole exome sequencing analyses, we identified a total of 287 variants in 55% of DRGs, of which 24 loss-of-function and 36 other predicted damaging variants were identified in 72% and 76% of BRCA1 and BRCA2 implicated cases, respectively. We also identified 60 variants of clinical interest in various known CPGs, including those involved in risk to other cancers, in 72% of BRCA1 and 60% of BRCA2 cases. The number of variants predicted to be deleterious in diverse DRGs raises questions about the interpretability of findings as panel testing expands beyond clinically established breast CPGs.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".