Confirmed germline pathogenic / likely-pathogenic variant in ETV6 (Thrombocytopenia 5, TH...

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

ID	`RF-ETV6-CONFIRMED-CARRIER`
Type	Red flag
Status	reviewed 2026-05-20 \| pending_clinical_signoff
Diseases	`DIS-AML` `DIS-B-ALL` `DIS-MDS-HR`
Sources	`SRC-ELN-AML-2022` `SRC-ESMO-MDS-2021` `SRC-NCCN-AML-2025`

Red Flag Origin

Definition	Confirmed germline pathogenic / likely-pathogenic variant in ETV6 (Thrombocytopenia 5, THC5; OMIM 616216). Most pathogenic variants are missense alleles in the ETS or PNT (pointed) domain that disrupt ETV6 transcription-factor function. Patient has had germline panel testing returned positive, ideally on buccal / fibroblast germline tissue. The carrier presents from infancy / childhood with mild-to- moderate isolated thrombocytopenia (platelet count typically 50-130 x10⁹/L, with red-cell macrocytosis a documented secondary feature) plus variably-penetrant bleeding diathesis. The malignancy risk profile is distinctive among the inherited-thrombocytopenia syndromes: pediatric B-cell acute lymphoblastic leukemia (B-ALL) is the dominant cancer phenotype, with ~25-30% cumulative incidence in confirmed-carrier pedigrees and onset typically in the first two decades of life. Adult onset MDS / A...
Clinical direction	investigate
Category	other

Trigger Logic

{
  "any_of": [
    {
      "finding": "germline_etv6_pathogenic_variant_confirmed",
      "value": true
    },
    {
      "finding": "thrombocytopenia_5_clinical_criteria_met",
      "value": true
    }
  ],
  "type": "lab_value"
}

Notes

Wave P confirmed-carrier surveillance pathway — germline ETV6 (Thrombocytopenia 5). Fires on documented germline ETV6 pathogenic variant positivity (typically PNT or ETS domain missense) OR documented THC5 clinical criteria (childhood-onset thrombocytopenia + ETV6-targeted genetic test positive + family pattern of B-ALL or inherited thrombocytopenia). Engine routes to PreventionPlan recommending: (a) IND-ETV6-CARRIER-SURVEILLANCE (standard) — CBC + smear q3-6 months lifelong from infancy through adulthood; BMA + flow cytometry + cytogenetics + myeloid NGS panel at any new / unexplained cytopenia, lymphadenopathy, or persistent cytological abnormality; pediatric oncology consultation on initial carrier confirmation in a child (B-ALL is the dominant childhood phenotype and early-detection planning differs from adult myeloid surveillance); annual review of bleeding history; cascade testing to first-degree relatives with documented buccal / fibroblast germline confirmation. (b) IND-ETV6-CARRIER-INTENSIFIED (aggressive) — standard protocol PLUS q3-month CBC + smear from infancy through age 20 (peak pediatric B-ALL incidence); BMA every 2-3 years from age 5 even without provoked indicat...

Used By

Indications

IND-ETV6-CARRIER-INTENSIFIED - IND-ETV6-CARRIER-INTENSIFIED
IND-ETV6-CARRIER-SURVEILLANCE - IND-ETV6-CARRIER-SURVEILLANCE