ACMG Class3
    PVS
  • PVS1
    VSSMP
    null variant
  • PS
  • PS1
    VSSMP
    literature: this AA exchange
  • PS2
    VSSMP
    confirmed de novo
  • PS3
    VSSMP
    supported by functional studies
  • PS4
    VSSMP
    prevalence in disease > controls
  • PM
  • PM1
    VSSMP
    variant in hotspot (missense)
  • PM2
    VSSMP
    rare; < 1:20.000 in ExAC
  • PM3
    VSSMP
    AR: trans with known pathogenic
  • PM4
    VSSMP
    protein length change
  • PM5
    VSSMP
    literature: AA exchange same pos
  • PM6
    VSSMP
    assumed de novo
  • PP
  • PP1
    VSSMP
    cosegregates in family
  • PP2
    VSSMP
    few missense in gene
  • PP3
    VSSMP
    predicted pathogenic ≥ 2
  • PP4
    VSSMP
    phenotype/pedigree match gene
  • PP5
    VSSMP
    reliable source: pathogenic
    BSA
  • BA1
    SASP
    allele frequency > 5%
  • BS
  • BS1
    SASP
    disease: allele freq. too high
  • BS2
    SASP
    observed in healthy individual
  • BS3
    SASP
    functional studies: benign
  • BS4
    SASP
    lack of segregation
  • BP
  • BP1
    SASP
    missense in truncation gene
  • BP2
    SASP
    other variant is causative
  • BP3
    SASP
    in-frame indel in repeat
  • BP4
    SASP
    prediction: benign
  • BP5
    SASP
    different gene in other case
  • BP6
    SASP
    reputable source: benign
  • BP7
    SASP
    silent, no splicing/conservation
Selected Criteria
Detailed Criteria Information
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