Confirmed germline pathogenic / likely-pathogenic variant in CEBPA — most commonly an N-t...

Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.

ID	`RF-CEBPA-CONFIRMED-CARRIER`
Тип	Тривожна ознака
Статус	переглянуто 2026-05-20 \| очікує клінічного підпису
Хвороби	`DIS-AML`
Джерела	`SRC-ELN-AML-2022` `SRC-ESMO-AML-2020` `SRC-NCCN-AML-2025`

Походження тривожної ознаки

Визначення	Confirmed germline pathogenic / likely-pathogenic variant in CEBPA — most commonly an N-terminal frameshift / nonsense allele that disrupts the p42 isoform while preserving p30 (the canonical familial AML germline configuration). Patient has had germline panel testing returned positive; the pedigree-suspicion phase is settled. No current personal AML diagnosis in the carrier being assessed (a current diagnosis routes to a treatment-track plan with carrier status driving donor-selection counseling and post-remission monitoring). Germline CEBPA carriers have a near-complete lifetime penetrance for AML — most series report ~80-100% by adulthood — with a typical disease pattern of a somatic CEBPA second hit acquired in cis (commonly the bZIP C-terminal in-frame indel) producing the AML clone. Prevention-persona RedFlag (KSS §20, confirmed-carrier surveillance pathway, distinct from a family...
Клінічний напрям	investigate
Категорія	other

Логіка спрацьовування

{
  "any_of": [
    {
      "finding": "germline_cebpa_pathogenic_variant_confirmed",
      "value": true
    },
    {
      "finding": "germline_cebpa_n_terminal_variant_confirmed",
      "value": true
    }
  ],
  "type": "lab_value"
}

Нотатки

Wave P confirmed-carrier surveillance pathway — germline CEBPA familial AML. Fires on documented germline CEBPA pathogenic variant positivity in an asymptomatic individual. Engine routes to PreventionPlan recommending: (a) IND-CEBPA-CARRIER-SURVEILLANCE (standard) — CBC + smear q3-6 months from diagnosis of carrier status, lifelong; BMA + myeloid NGS at any suspicious cytopenia, persistent blast on smear, or unexplained leukocytosis; annual molecular check for the inherited variant allele-burden if a sensitive assay is available; cascade germline testing to first-degree relatives with documented buccal / fibroblast germline confirmation (NOT blood-only, to avoid somatic clone contamination of result). (b) IND-CEBPA-CARRIER-INTENSIFIED (aggressive) — standard protocol PLUS HLA typing on cohort + sibling early to map donor candidates; q3-month CBC + smear (instead of q6); BMA at clinical milestones (every 2-3 years from age 20+) even without provoked indication; preemptive consultation with a hereditary-myeloid-program transplant team so that go-to- transplant decisions at AML diagnosis are not delayed. STUB pending two-Clinical-Co-Lead signoff per CHARTER §6.1 dev-mode exemption. P...

Де використовується

Indications

IND-CEBPA-CARRIER-INTENSIFIED - IND-CEBPA-CARRIER-INTENSIFIED
IND-CEBPA-CARRIER-SURVEILLANCE - IND-CEBPA-CARRIER-SURVEILLANCE