Documentation / Structural Variants / Input and Scope

Input and Scope

The current production workflow reads structural-variant and copy-number records from a compatible VCF. It recognizes the normalized event types DEL, DUP, INV, INS, BND, and CNV from standard VCF fields or symbolic alleles.

Sequence-resolved deletions and insertions can also enter structural-variant processing when their reference-versus-alternate length difference is at least 50 base pairs. Smaller sequence changes remain in the small-variant path.

Fields Used When Available

Event type and alternate allele representation.

Start, end, and structural-variant length. Length is represented as a magnitude so deletion sign conventions do not change interpretation.

Copy number, genotype, and derived zygosity.

Breakpoint precision and confidence intervals.

Paired-read, split-read, and other call-support values supplied by the VCF.

Framework Ownership

Every supported record is assigned to one interpretation owner. This prevents the same event from receiving competing automated verdicts from multiple frameworks.

Copy-number loss

When: Deletion or a reported copy state below the reference state

Result: ClinGen/ACMG Riggs 2020 loss framework

Copy-number gain

When: Duplication or a reported copy state above the reference state, after loss has been excluded

Result: ClinGen/ACMG Riggs 2020 gain framework

Other eligible nuclear SV

When: Non-mitochondrial, non-reference event with an annotated gene and no copy-number loss or gain ownership

Result: Nuclear ACMG/AMP Variant Analysis framework

Unsupported record

When: No safe framework owner can be established from the available fields

Result: No automated verdict; the reason remains recorded for review

Caller-Neutral Processing

Folklore does not select interpretation rules by caller brand. Different callers may populate different VCF fields, so missing optional evidence can reduce what the platform can establish, but it does not create a caller-specific classification path.

Current Boundaries

VCF is the production input for this workflow; TSV and BEDPE are not current Folklore analysis inputs.

For a multi-allelic record, structural normalization follows the first alternate allele. Submit unambiguous, normalized records for clinical use.

The analysis uses the first sample represented by the primary single-sample Variant Analysis workflow.

A missing end coordinate can limit interval-based evidence, particularly for insertions and breakends.

A missing gene annotation, a hom-ref genotype, or an unsupported mitochondrial structural event can prevent automated framework assignment.

Repeat expansions and somatic tumor events are outside this germline interpretation workflow.

Interpretation and Limitations

How structural and copy-number evidence is presented and where clinical review remains essential.