Confirmed germline pathogenic / likely-pathogenic variant in ANKRD26 (Thrombocytopenia 2,...

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

ID	`RF-ANKRD26-CONFIRMED-CARRIER`
Тип	Тривожна ознака
Статус	переглянуто 2026-05-20 \| очікує клінічного підпису
Хвороби	`DIS-AML` `DIS-MDS-HR`
Джерела	`SRC-ELN-AML-2022` `SRC-ESMO-MDS-2021` `SRC-NCCN-AML-2025`

Походження тривожної ознаки

Визначення	Confirmed germline pathogenic / likely-pathogenic variant in ANKRD26 (Thrombocytopenia 2, THC2; OMIM 188000). Most pathogenic variants cluster in the 5′-untranslated region (the ANKRD26 5′UTR hotspot, chr10:27,389-27,420), disrupting RUNX1 / FLI1-mediated repression and producing a persistent ANKRD26 over-expression phenotype during megakaryopoiesis. Patient has had germline panel testing returned positive, ideally on buccal / fibroblast germline tissue. The carrier presents from birth / childhood with mild-to-moderate isolated thrombocytopenia (platelet count 40-120 x10⁹/L typically) plus a variably-penetrant bleeding diathesis (mild mucocutaneous bleeding, surgical bleeding risk). Lifetime risk of myeloid malignancy (MDS or AML) is documented as ~5-10% in cohort series and is lower than in classic RUNX1 / FPD/AML pedigrees, but enough to mandate lifelong surveillance — the malignant p...
Клінічний напрям	investigate
Категорія	other

Логіка спрацьовування

{
  "any_of": [
    {
      "finding": "germline_ankrd26_pathogenic_variant_confirmed",
      "value": true
    },
    {
      "finding": "thrombocytopenia_2_clinical_criteria_met",
      "value": true
    }
  ],
  "type": "lab_value"
}

Нотатки

Wave P confirmed-carrier surveillance pathway — germline ANKRD26 (Thrombocytopenia 2). Fires on documented germline ANKRD26 pathogenic variant positivity (typically the 5′UTR hotspot) OR documented THC2 clinical criteria (lifelong moderate thrombocytopenia + RUNX1-negative + ANKRD26-targeted genetic test positive). Engine routes to PreventionPlan recommending: (a) IND-ANKRD26-CARRIER-SURVEILLANCE (standard) — CBC + smear q6 months lifelong from carrier confirmation; BMA + myeloid NGS panel + cytogenetics at any clinically-concerning change (new cytopenia in another lineage, persistent dysplasia on smear, unexplained increase in WBC); annual review of bleeding history + medication review (avoid antiplatelet drugs when feasible); cascade testing to first-degree relatives. (b) IND-ANKRD26-CARRIER-INTENSIFIED (aggressive) — standard protocol PLUS BMA every 3-5 years even without provoked indication; q3-month CBC during pregnancy / perioperative windows; preemptive HLA typing on candidate sibling donors with germline ANKRD26 screening required before any future transplant use; structured-bleeding-risk plan for major surgery / obstetric care. STUB pending two-Clinical-Co-Lead signoff pe...

Де використовується

Indications

IND-ANKRD26-CARRIER-INTENSIFIED - IND-ANKRD26-CARRIER-INTENSIFIED
IND-ANKRD26-CARRIER-SURVEILLANCE - IND-ANKRD26-CARRIER-SURVEILLANCE