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Documentation / Structural Variants

Structural Variants and CNVs

Structural-variant analysis is part of Folklore's production Variant Analysis pipeline. It normalizes compatible VCF calls, gathers structural and copy-number evidence, and assigns each supported record to exactly one interpretation framework.

The workflow is caller-neutral: interpretation depends on the normalized event and available evidence, not on the name of the upstream calling tool. Missing fields remain visible as evidence limitations rather than being inferred without support.

Interpretation, Not Variant Calling

Folklore starts from calls already present in the submitted VCF. Read alignment, structural-variant discovery, breakpoint assembly, and upstream caller validation remain the responsibility of the laboratory workflow.

Production Workflow

1

Read the submitted call

Folklore consumes compatible structural-variant records from the uploaded VCF. It does not call structural variants from sequencing reads.

2

Normalize the event

Recognized calls are represented consistently as deletion, duplication, inversion, insertion, breakend, or copy-number variant, with genomic span and copy state when supplied.

3

Annotate clinical context

The pipeline evaluates gene and exon overlap, dosage-sensitive regions, predicted dosage sensitivity, population overlap, and available call-quality evidence.

4

Assign one framework

Constitutional copy-number loss or gain is assigned to the Riggs 2020 framework. Other eligible nuclear events are handled by the nuclear Variant Analysis framework.

5

Present an auditable result

The result preserves the owning framework, classification, contributing evidence, genomic content, population context, and limitations for clinical review.

What the Result Can Show

Event summary

Type, chromosome, start and end coordinates, span, copy state, zygosity, and precision when available.

Classification

A five-tier result and the framework that produced it when the record is eligible for automated interpretation.

Genomic impact

Overlapping genes, exons, dosage-sensitive regions, and per-gene dosage evidence.

Population context

Type-compatible overlap against local structural-variant population references.

Call evidence

Available precision, confidence interval, paired-read, split-read, and related quality fields.

Audit trail

Human-readable evidence criteria and a machine-readable breakdown for supported CNV classifications.

Clinical Boundary

Structural-variant classification is clinical decision support. Breakpoint uncertainty, assay coverage, mosaicism, inheritance, phenotype fit, and orthogonal confirmation can materially change interpretation and require qualified review.

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