ACMG_PVS1:
  description: >
    Null variants (IMPACT = HIGH) in genes where loss-of-function causes disease.
    Includes homozygous variants, dominant inheritance, and compound heterozygous cases.
    Compound heterozygosity is considered when both variants are HIGH impact. WARNING: Not phase checked.
  logic: "or"
  conditions:
    - condition:
        field: IMPACT
        value: "HIGH"
        operator: "=="
    - condition:
        field: genotype
        value: 2
        operator: "=="
    - condition:
        field: Inheritance
        value: "AD"
        operator: "=="
    - condition:
        group_by:
          - sample
          - SYMBOL
        count: ">=2"
        additional_criteria:
          field: comp_het_flag
          value: 1
          operator: "=="

ACMG_PS1:
  description: >
    The same amino acid change was a previously established pathogenic variant regardless of nucleotide change. 
  terms:
    - pathogenic
  fields:
    clinical_significance: CLIN_SIG
  logic: "or"

ACMG_PS3:
  description: >
    Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.
    User defined - disease panel ineritance pattern matching genotype. 
  logic: "or"
  conditions:
    - condition:
        field: genotype
        value: 1
        operator: "=="
        additional_criteria:
          field: Inheritance
          values:
            - AD
            - AD/AR
    - condition:
        field: genotype
        value: 2
        operator: "=="
        additional_criteria:
          field: Inheritance
          values:
            - AD
            - AD/AR
            - AR
            - XL
            - XLR

ACMG_PS5:
  description: >
    Compound heterozygosity with at least one HIGH impact variant. This is not phase checked.
  logic: "and"
  conditions:
    - condition:
        field: IMPACT
        value: "HIGH"
        operator: "=="
    - condition:
        group_by: 
          - sample
          - SYMBOL
        count: ">1"


ACMG_PM2:
  description: >
    Absent from controls (or at extremely low frequency if recessive) in gnmonAD, 1000 Genomes Project, etc.
  logic: "and"
  conditions:
    - condition:
        field: gnomAD_AF
        value: 1e-6
        operator: "<"

ACMG_PM3:
  description: >
    For recessive disorders, detected in trans with a pathogenic variant.
    Some redundancy with PS5, as rare disease cohort filtering considers IMPACT == HIGH as pathogenic.
  logic: "and"
  conditions:
    - condition:
        field: comp_het_flag
        value: 1
        operator: "=="
    - condition:
        field: ACMG_PS1
        value: "PS1"
        operator: "=="
        logic: "or"
    - condition:
        field: ACMG_PS5
        value: "PS5"
        operator: "=="