Family pedigree pattern suggestive of germline RAD51C or RAD51D heterozygous carrier stat...

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

ID	`RF-RAD51C-D-FAMILY-HISTORY-SUSPICION`
Type	Red flag
Status	reviewed 2026-05-19 \| pending_clinical_signoff
Diseases	`DIS-BREAST` `DIS-OVARIAN`
Sources	`SRC-NCCN-BREAST-2025` `SRC-NCCN-GENETIC-FAMILIAL-BREAST-OVARIAN-2025` `SRC-NCCN-OVARIAN-2025`

Red Flag Origin

Definition	Family pedigree pattern suggestive of germline RAD51C or RAD51D heterozygous carrier state in an asymptomatic individual who has NOT yet had multi-gene panel testing. RAD51C/D are RAD51 paralogs essential for homologous-recombination repair; carriers approach BRCA-level ovarian penetrance (lifetime ovarian cancer ~10-15% RAD51C, ~12-20% RAD51D; RR ~5.9 and ~6.6 respectively). Triggers include any of (a) first- or second-degree relative with a confirmed RAD51C or RAD51D pathogenic / likely-pathogenic variant; (b) family-history cluster of multiple ovarian / fallopian-tube / primary peritoneal carcinomas (≥2 first/second-degree affected relatives) with negative BRCA1/2 testing in affected relative — RAD51C/D are the most common moderate-penetrance findings (after BRIP1) in BRCA-negative ovarian-predominant pedigrees; (c) BRCA-negative HBOC-spectrum pedigree with predominantly ovarian rath...
Clinical direction	investigate
Category	other

Trigger Logic

{
  "any_of": [
    {
      "finding": "family_rad51c_or_rad51d_known_pathogenic_variant",
      "value": true
    },
    {
      "finding": "family_multiple_ovarian_brca_negative_two_or_more",
      "value": true
    },
    {
      "finding": "family_brca_negative_hboc_ovarian_predominant_high_grade_serous",
      "value": true
    },
    {
      "finding": "family_multiple_high_grade_serous_ovarian_multi_generation",
      "value": true
    }
  ],
  "type": "lab_value"
}

Notes

v0.3 Wave M suspicion variant — pre-testing family-history- suspicion counterpart to RF-RAD51C-D-CONFIRMED-CARRIER. Fires when family pedigree pattern suggests RAD51C or RAD51D carrier state but germline panel testing has not yet been completed. Standard pathway = referral for genetic counseling + multi-gene HBOC panel covering BRCA1/2 + RAD51C/D + BRIP1 minimum. If panel returns positive for RAD51C or RAD51D, the patient transitions to the RF-RAD51C-D-CONFIRMED-CARRIER pathway with NCCN-endorsed RRSO at completed childbearing or age 45-50 (RAD51C/D approach BRCA-level penetrance), individualised breast surveillance with MRI consideration in elevated-family-history subset, and PARP inhibitor relevance for any future ovarian-cancer diagnosis (PROfound + GEN-ALL trials). Distinct trigger findings from the confirmed-carrier RF (carrier RF fires on `germline_rad51c_ pathogenic_variant_confirmed` / `germline_rad51d_pathogenic_ variant_confirmed`; suspicion RF fires on family-history-based findings only). STUB pending two-Clinical-Co-Lead signoff per CHARTER §6.1 dev-mode.

Used By

Indications

IND-RAD51C-D-SUSPICION-PREVENTION-EMPIRICAL-SURVEILLANCE - IND-RAD51C-D-SUSPICION-PREVENTION-EMPIRICAL-SURVEILLANCE
IND-RAD51C-D-SUSPICION-PREVENTION-TESTING - IND-RAD51C-D-SUSPICION-PREVENTION-TESTING