Documentation / Screening
Screening
After Variant Analysis assigns each variant an ACMG category, a clinician still needs a focused review queue. Screening applies a multi-dimensional prioritization layer to Pathogenic, Likely Pathogenic, and optionally VUS findings within the selected gene scope.
Screening orders the available candidates by configured clinical context and retains a score breakdown and justification for review. The number of high-priority results depends on the case, selected mode, available phenotype data, and configured filters.
How Screening Works
Resolve the Gene Scope
Selected panels and custom genes define which genes are screened. Without either, Folklore uses its built-in fallback set rather than loading every gene.
Calculate Component Scores
Each variant is evaluated across seven dimensions: gene constraint, computational deleteriousness, phenotype relevance, dosage sensitivity, consequence severity, compound heterozygote potential, and age-appropriate gene prioritization.
Apply Clinical Boosts
Patient-specific context (ACMG class, phenotype match tier, ethnicity, family history, sex-linked inheritance, consanguinity, pregnancy status) adds additional priority boosts.
Assign Tiers
Variants are ranked by their final score and explicit priority rules, then assigned to one of four review tiers. Tier 1 is the highest-priority review queue.
Key Design Principles
The seven component scores, selected clinical boosts, final score, tier, and human-readable justification are retained for review. Some context contributions affect the total without appearing as separate output columns.
Pathogenic and Likely Pathogenic classifications contribute a strong prioritization boost, but final tier assignment remains inheritance-aware. A heterozygous finding in an autosomal-recessive gene can be demoted when no compound-heterozygous partner is supported.
Scoring adapts to clinical context. A neonatal screening case uses different weights than an adult proactive screening case. Diagnostic mode with HPO terms emphasizes phenotype matching.
Component and final scores are bounded to 0.0-1.0. They are prioritization values, not probabilities of pathogenicity or clinical actionability.
Screening runs after classification and records the applied mode, component scores, boosts, and final tier for audit and review.
Screening vs. Classification
Classification assigns the evidence-based ACMG class. Screening is a separate prioritization layer that orders findings for review using the selected mode and patient context. A screening tier does not modify or override the underlying ACMG classification.
In This Section
Scoring Components
Seven dimensions of variant scoring: constraint, deleteriousness, phenotype, dosage, consequence, compound het, and age relevance.
Tier System
Four-tier priority ranking with clinical actionability labels and boost mechanisms.
Screening Modes
Diagnostic, neonatal, pediatric, proactive adult, carrier, and pharmacogenomics modes.
Age-Aware Prioritization
How patient age influences scoring weights and gene relevance from neonatal through elderly.
Gene Panels and Custom Genes
How panels define the genes in scope and contribute curated disease, age, priority, and ClinGen context.