Germline PALB2 pathogenic variant — BRCA2's recruitment partner; biallelic LOF produces a...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-PAN-PALB2-PARPI-CANDIDATE`
Type	Red flag
Status	reviewed 2026-04-29 \| pending_clinical_signoff
Diseases	`DIS-BREAST` `DIS-PDAC` `DIS-PROSTATE`
Sources	`SRC-NCCN-BREAST-2025` `SRC-NCCN-PANCREATIC-2025` `SRC-NCCN-PROSTATE-2025` `SRC-PROFOUND-DEBONO-2020`

Red Flag Origin

Definition	Germline PALB2 pathogenic variant — BRCA2's recruitment partner; biallelic LOF produces an HRR-deficient phenotype. Pan-tumor PARPi candidate signal weaker than gBRCA1/2 but emerging. Disease applicability: breast (lifetime risk ~35-55%, NCCN high-penetrance — PARPi off-label / investigational), PDAC (~3-5x baseline risk, POLO label is gBRCA-only but PALB2 frequently grouped clinically), prostate mCRPC (cohort-B in PROfound HRR-non-BRCA/ATM — smaller absolute olaparib benefit but PARPi remains an option per NCCN 2025). Genetic counseling + cascade testing of first-degree relatives required.
Clinical direction	intensify
Category	high-risk-biology

Trigger Logic

{
  "any_of": [
    {
      "finding": "palb2_germline",
      "value": "pathogenic"
    },
    {
      "finding": "palb2_status",
      "value": "pathogenic"
    },
    {
      "finding": "germline_palb2",
      "value": "pathogenic"
    },
    {
      "finding": "palb2_pathogenic",
      "value": true
    }
  ],
  "type": "biomarker"
}

Notes

References BIO-PALB2-GERMLINE. Surveillance recommendations: enhanced breast screening (annual MRI from age 30), pancreatic surveillance per CAPS consortium when family history present. RF distinct from RF-BREAST-BRCA-GERMLINE-ACTIONABLE (BRCA-specific) and RF-PROSTATE-HIGH-RISK-BIOLOGY (which captures HRR pathway broadly via hrr_pathway_mutation key but does not key on palb2_germline directly). No NCCN hereditary-cancer panel source exists in KB — using disease-specific NCCN sources instead; flagged in commit body.

Used By

Indications

IND-PROSTATE-MCRPC-2L-CABAZITAXEL - IND-PROSTATE-MCRPC-2L-CABAZITAXEL
IND-PROSTATE-MCRPC-2L-DOCETAXEL - IND-PROSTATE-MCRPC-2L-DOCETAXEL