Confirmed germline pathogenic / likely-pathogenic variant in the BLM gene — Bloom syndrom...

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

ID	`RF-BLM-CONFIRMED-CARRIER`
Type	Red flag
Status	reviewed 2026-05-20 \| pending_clinical_signoff
Diseases	`DIS-BREAST` `DIS-CRC`
Sources	`SRC-CLEARY-BLM-2003` `SRC-NCCN-COLON-2025` `SRC-NCCN-GENETIC-FAMILIAL-CRC-2025`

Red Flag Origin

Definition	Confirmed germline pathogenic / likely-pathogenic variant in the BLM gene — Bloom syndrome carrier status. Biallelic BLM inactivation causes Bloom syndrome (BS) — autosomal-recessive chromosomal- instability disorder with severe growth restriction, photosensitive facial erythema, immunodeficiency, and dramatically elevated risk of a broad spectrum of cancers (CRC, leukemia, lymphoma, breast, skin) with median age of cancer diagnosis ~25-30 years. Heterozygous (carrier) status — the focus of this RedFlag — confers a modest signal for colorectal cancer (RR ~1.5-2.0) and possibly breast cancer (RR ~1.5; evidence less consistent). The Ashkenazi Jewish founder variant c.2207_2212delinsTAGATTC (p.Tyr736LeufsTer5; also reported as p.Tyr736X / BLM-Ash) has population carrier frequency ~1% in Ashkenazi Jews, making BLM carrier testing routine on Ashkenazi preconception panels and population-rele...
Clinical direction	investigate
Category	other

Trigger Logic

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

Notes

v0.3 wave-N niche moderate-penetrance carrier pathway — BLM heterozygosity. Fires on documented germline BLM pathogenic variant positivity in an asymptomatic individual. Engine routes to PreventionPlan recommending: (a) IND-BLM-CARRIER-SURVEILLANCE (standard) — CRC screening with colonoscopy q5y from age 40 (or 10y before earliest familial CRC diagnosis); breast cancer awareness + population-cadence screening at standard ages; cascade testing of first-degree relatives; reproductive counseling for partners who are also carriers (biallelic Bloom syndrome risk to offspring). (b) IND-BLM-CARRIER-OBSERVATION (alternative) — population-cadence screening only (CRC q10y from age 45 per USPSTF). Counsel that this is sub-optimal vs. mildly intensified surveillance comparator. Per CHARTER §11 patient-autonomy framing. Ashkenazi founder allele context: c.2207_2212delinsTAGATTC (p.Tyr736X / BLM-Ash) is the dominant pathogenic variant in Ashkenazi Jewish populations (population carrier frequency ~1% — approximately 1 in 100). Routine inclusion on Ashkenazi preconception panels alongside BRCA1/2 founder variants. NCCN Genetic/Familial High-Risk CRC includes BLM in moderate-penetrance CRC-gene pa...

Used By

Indications

IND-BLM-CARRIER-OBSERVATION - IND-BLM-CARRIER-OBSERVATION
IND-BLM-CARRIER-SURVEILLANCE - IND-BLM-CARRIER-SURVEILLANCE

Sources

SRC-CLEARY-BLM-2003 - Heterozygosity for the BLM(Ash) mutation and cancer risk