Confirmed germline pathogenic / likely-pathogenic variant in RAD51C OR RAD51D — RAD51 par...

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

ID	`RF-RAD51C-D-CONFIRMED-CARRIER`
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	Confirmed germline pathogenic / likely-pathogenic variant in RAD51C OR RAD51D — RAD51 paralogs essential for homologous-recombination repair, partners of BRCA1/BRCA2 in the HR complex. Heterozygous carriers have moderate-to-high-penetrance ovarian cancer risk (RR ~5.9 RAD51C, RR ~6.6 RAD51D; lifetime ovarian cancer ~10-15% RAD51C, ~12-20% RAD51D — approaching BRCA1/2 levels). Modest breast cancer signal (RR ~1.5-2.0 for RAD51C; some evidence higher for triple-negative subset). Biallelic RAD51C is Fanconi anemia complementation group O; biallelic RAD51D more variable. Less common multi-gene panel finding (~0.5-1% of unselected ovarian cancer cohorts). Patient has confirmed positive germline test in RAD51C or RAD51D; no current personal cancer diagnosis in the carrier being assessed. Prevention-persona RedFlag (§20, v0.3 moderate-penetrance ovarian gene expansion).
Clinical direction	investigate
Category	other

Trigger Logic

{
  "any_of": [
    {
      "finding": "germline_rad51c_pathogenic_variant_confirmed",
      "value": true
    },
    {
      "finding": "germline_rad51d_pathogenic_variant_confirmed",
      "value": true
    },
    {
      "finding": "germline_rad51c_likely_pathogenic_variant",
      "value": true
    },
    {
      "finding": "germline_rad51d_likely_pathogenic_variant",
      "value": true
    }
  ],
  "type": "lab_value"
}

Notes

Prevention-persona RedFlag for RAD51C/RAD51D heterozygous carriers. Approaches BRCA-level ovarian penetrance — NCCN endorses RRSO at completed childbearing or age 45-50. Breast surveillance: individualised by family history; consider annual MRI in additional- risk subset. Olaparib PARP inhibitor active in RAD51C/D-mutant established ovarian cancer (PROfound + GEN-ALL trials). STUB pending two-Co-Lead signoff per CHARTER §6.1 dev-mode.

Used By

Indications

IND-RAD51C-D-CARRIER-PREVENTION-OBSERVATION - IND-RAD51C-D-CARRIER-PREVENTION-OBSERVATION
IND-RAD51C-D-CARRIER-PREVENTION-SURVEILLANCE - IND-RAD51C-D-CARRIER-PREVENTION-SURVEILLANCE
IND-RAD51C-D-SUSPICION-PREVENTION-TESTING - IND-RAD51C-D-SUSPICION-PREVENTION-TESTING

Red flag

RF-RAD51C-D-FAMILY-HISTORY-SUSPICION - Family pedigree pattern suggestive of germline RAD51C or RAD51D heterozygous carrier stat...