Confirmed germline pathogenic / likely-pathogenic variant in the NBN gene (also known as...

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

ID	`RF-NBN-CONFIRMED-CARRIER`
Type	Red flag
Status	reviewed 2026-05-20 \| pending_clinical_signoff
Diseases	`DIS-BREAST`
Sources	`SRC-BOGDANOVA-NBN-2008` `SRC-NCCN-BREAST-2025` `SRC-NCCN-GENETIC-FAMILIAL-BREAST-OVARIAN-2025`

Red Flag Origin

Definition	Confirmed germline pathogenic / likely-pathogenic variant in the NBN gene (also known as NBS1) — Nijmegen Breakage Syndrome carrier status. Biallelic NBN inactivation (homozygous or compound-heterozygous) causes Nijmegen Breakage Syndrome (NBS) — autosomal-recessive chromosomal- instability disorder with microcephaly, immunodeficiency, growth failure, and dramatically elevated lymphoid-malignancy risk (~40% lifetime by age 20). Heterozygous (carrier) status — the focus of this RedFlag — confers moderate-penetrance breast-cancer risk (RR ~2.0-3.0, lifetime ~20-25%) and a more modest signal for lymphoma / prostate cancer. The Slavic founder variant c.657del5 (p.Lys219AsnfsTer16) is population- prevalent in Polish, Ukrainian, Czech, and other Eastern-European populations (~0.5-1% carrier frequency), making NBN moderate-penetrance testing particularly relevant for Ukrainian familial breast-...
Clinical direction	investigate
Category	other

Trigger Logic

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

Notes

v0.3 wave-N niche moderate-penetrance carrier pathway — NBN heterozygosity. Fires on documented germline NBN pathogenic variant positivity in an asymptomatic individual. Engine routes to PreventionPlan recommending: (a) IND-NBN-CARRIER-SURVEILLANCE (standard) — annual breast MRI from age 30; annual mammography from age 30-35 (alternating with MRI q6mo); clinical breast exam q6-12mo from age 25; cascade testing of first-degree relatives; reproductive counseling for partners who are also carriers (biallelic offspring NBS risk). (b) IND-NBN-CARRIER-OBSERVATION (alternative) — population-cadence breast screening only; counsel that this is sub-optimal vs. intensified MRI surveillance comparator. Per CHARTER §11 patient-autonomy framing. Slavic founder allele context: c.657del5 (p.Lys219AsnfsTer16) is the dominant pathogenic variant in Polish, Ukrainian, Czech, Slovak, and other Eastern-European populations (population carrier frequency ~0.5-1%). The OpenOnco Ukrainian patient cohort therefore has a meaningful prior probability for NBN heterozygote breast-cancer risk beyond what NCCN's North-American-cohort base rates suggest. NCCN Genetic/Familial High-Risk Breast/Ovarian acknowledges...

Used By

Indications

IND-NBN-CARRIER-OBSERVATION - IND-NBN-CARRIER-OBSERVATION
IND-NBN-CARRIER-SURVEILLANCE - IND-NBN-CARRIER-SURVEILLANCE

Sources

SRC-BOGDANOVA-NBN-2008 - Nijmegen Breakage Syndrome mutations and risk of breast cancer