qv_set_id: qv_acmg_sf_v3_3_20250828
version: 1.0.0
title: ACMG secondary findings
description: Report pathogenic or likely pathogenic variants in ACMG SF v3.3 genes with inheritance-aware rules and technical QC.
metadata:
  created: '2025-08-28'
  authors: SwitzerlandOmics
  tags:
    - ACMG
    - SF
    - Clinical
    - QC
  acmg_sf_version: v3.3
  schema_fields: SYMBOL,Inheritance,sex,genotype,IMPACT,ACMG_CLASS,SVTYPE,CNV_EXON_COUNT,DP,GQ,AB,TTN_PSI
filters:
  region_include:
    description: Limit to ACMG SF genes v3.3
    logic: keep_if
    field: OVERLAP(targets.acmg_sf.v3_3.bed)
    operator: '>='
    value: 1
  consent_sf:
    description: Patient opted in to receive secondary findings
    logic: keep_if
    field: consent_sf_return
    operator: '=='
    value: 1
  min_dp:
    description: Minimum read depth
    logic: keep_if
    field: DP
    operator: '>='
    value: 10
  min_gq:
    description: Minimum genotype quality
    logic: keep_if
    field: GQ
    operator: '>='
    value: 20
criteria:
  SF_P_or_LP:
    conditions:
      - group: any_of:start
      - field: ACMG_CLASS
        operator: '=='
        value: P
      - field: ACMG_CLASS
        operator: '=='
        value: LP
      - group: any_of:end
    description: Variant classified as pathogenic or likely pathogenic
    logic: and
  SF_AD:
    conditions:
      - group: any_of:start
      - field: Inheritance
        operator: '=='
        value: AD
      - field: Inheritance
        operator: '=='
        value: XLD
      - group: any_of:end
      - group: any_of:start
      - field: genotype
        operator: '=='
        value: 1
      - field: genotype
        operator: '=='
        value: 2
      - group: any_of:end
      - field: ACMG_CLASS
        operator: '=='
        value: P
      - field: ACMG_CLASS
        operator: '=='
        value: LP
    description: Autosomal dominant or X linked dominant. One qualifying allele is sufficient.
    logic: and
  SF_XL_male:
    conditions:
      - field: Inheritance
        operator: '=='
        value: XLR
      - field: sex
        operator: '=='
        value: M
      - field: genotype
        operator: '=='
        value: 1
      - group: any_of:start
      - field: ACMG_CLASS
        operator: '=='
        value: P
      - field: ACMG_CLASS
        operator: '=='
        value: LP
      - group: any_of:end
    description: X linked recessive. Male hemizygous.
    logic: and
  SF_AR_homozygous:
    conditions:
      - field: Inheritance
        operator: '=='
        value: AR
      - field: genotype
        operator: '=='
        value: 2
      - group: any_of:start
      - field: ACMG_CLASS
        operator: '=='
        value: P
      - field: ACMG_CLASS
        operator: '=='
        value: LP
      - group: any_of:end
    description: Autosomal recessive. Homozygous P or LP variant.
    logic: and
  SF_AR_comphet:
    conditions:
      - field: Inheritance
        operator: '=='
        value: AR
      - field: genotype
        operator: '=='
        value: 1
      - group: any_of:start
      - field: ACMG_CLASS
        operator: '=='
        value: P
      - field: ACMG_CLASS
        operator: '=='
        value: LP
      - group: any_of:end
      - group_by:
          - sample
          - SYMBOL
        count: '>=2'
    description: Autosomal recessive. Compound heterozygous P or LP variants. Phase check recommended.
    logic: and
  SF_TTN_truncating_psi90:
    conditions:
      - field: SYMBOL
        operator: '=='
        value: TTN
      - field: IMPACT
        operator: '=='
        value: HIGH
      - field: TTN_PSI
        operator: '>='
        value: 0.9
      - group: any_of:start
      - field: genotype
        operator: '=='
        value: 1
      - field: genotype
        operator: '=='
        value: 2
      - group: any_of:end
      - group: any_of:start
      - field: ACMG_CLASS
        operator: '=='
        value: P
      - field: ACMG_CLASS
        operator: '=='
        value: LP
      - group: any_of:end
    description: TTN truncating in exons with high cardiac expression (PSI >= 0.9).
    logic: and
  SF_SV_CNV:
    conditions:
      - group: any_of:start
      - field: SVTYPE
        operator: '=='
        value: DEL
      - field: SVTYPE
        operator: '=='
        value: DUP
      - group: any_of:end
      - field: CNV_EXON_COUNT
        operator: '>='
        value: 1
      - group: any_of:start
      - field: ACMG_CLASS
        operator: '=='
        value: P
      - field: ACMG_CLASS
        operator: '=='
        value: LP
      - group: any_of:end
    description: P or LP exon level CNVs in SF genes.
    logic: and
notes:
  - Assumes ACMG_CLASS values P or LP. If not available, add gene specific LoF rules separately.
  - Assumes targets.acmg_sf.v3_3.bed defines the ACMG SF v3.3 gene set.
  - Consent filter is optional. Remove if not applicable.