Family pedigree pattern suggestive of germline CHEK2 heterozygous carrier state in an asy...

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

ID	`RF-CHEK2-FAMILY-HISTORY-SUSPICION`
Type	Red flag
Status	reviewed 2026-05-19 \| pending_clinical_signoff
Diseases	`DIS-BREAST` `DIS-CRC` `DIS-PROSTATE`
Sources	`SRC-NCCN-BREAST-2025` `SRC-NCCN-GENETIC-FAMILIAL-BREAST-OVARIAN-2025` `SRC-NCCN-GENETIC-FAMILIAL-CRC-2025`

Red Flag Origin

Definition	Family pedigree pattern suggestive of germline CHEK2 heterozygous carrier state in an asymptomatic individual who has NOT yet had multi-gene panel testing. CHEK2 c.1100delC is one of the most common moderate-penetrance variants in European-ancestry populations (~1.5% carrier frequency). Triggers include any of (a) first- or second-degree relative with a confirmed CHEK2 pathogenic / likely- pathogenic variant (most commonly c.1100delC); (b) family-history cluster of breast cancer (moderate-penetrance ~RR 2-3) plus colorectal cancer in close relatives — a recognized CHEK2 multi- cancer signature; (c) family history of multiple high-grade prostate cancers (CHEK2 c.1100delC has documented high-grade / metastatic prostate enrichment); (d) Slavic/Baltic/Polish/Ashkenazi ancestry combined with personal or family history of breast, colorectal, prostate, or thyroid cancer — CHEK2 c.1100delC has...
Clinical direction	investigate
Category	other

Trigger Logic

{
  "any_of": [
    {
      "finding": "family_chek2_known_pathogenic_variant",
      "value": true
    },
    {
      "finding": "family_breast_and_colorectal_cluster",
      "value": true
    },
    {
      "finding": "family_high_grade_prostate_multiple",
      "value": true
    },
    {
      "finding": "family_slavic_baltic_polish_ashkenazi_with_breast_or_crc_or_prostate",
      "value": true
    }
  ],
  "type": "lab_value"
}

Notes

v0.3 Wave M suspicion variant — pre-testing family-history- suspicion counterpart to RF-CHEK2-CONFIRMED-CARRIER. Fires when family pedigree pattern suggests CHEK2 carrier state but germline panel testing has not yet been completed. Standard pathway = referral for genetic counseling + multi-gene panel testing covering BRCA1/2 + relevant moderate-penetrance genes (CHEK2 is on every HBOC panel; if CRC family history dominates, an expanded CRC-inclusive panel covering Lynch + APC + MUTYH should be ordered). If panel returns positive for CHEK2, the patient transitions to the RF-CHEK2-CONFIRMED-CARRIER pathway with variant-specific surveillance (truncating > splice > missense risk tiers). Distinct trigger findings from the confirmed- carrier RF (carrier RF fires on `germline_chek2_pathogenic_ variant_confirmed` / `germline_chek2_1100delc_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-CHEK2-SUSPICION-PREVENTION-EMPIRICAL-SURVEILLANCE - IND-CHEK2-SUSPICION-PREVENTION-EMPIRICAL-SURVEILLANCE
IND-CHEK2-SUSPICION-PREVENTION-TESTING - IND-CHEK2-SUSPICION-PREVENTION-TESTING