ACMG Variant Pathogenicity Statement Example

Description:

• The Pathogenicity Statement data below adds instructive annotations to this Simple Test Fixtures Example from ClinGen’s “ClinVar-GKS” implementation of the Variant Pathogenicity Statement (ACMG 2015) Profile.

• The annotations are intended to help readers better understand the structure, semantics, and utility of VA-Spec models.

• The example itself covers a subset of data from the ClinVar SCV000778434.1 record - which reports that “the KCNQ4 variant NM_004700.4:c.803CCT[1] is pathogenic for Autosomal dominant nonsyndromic hearing loss 2A”.

• Note that the data below omits a full representation of the CategoricalVariation that is the subject of the Statement - as this is the remit of the CatVRS specification.

Data:

SCV000778434.1:
  id: SCV000778434.1
  type: Statement+
  proposition:+
    id: ex:Proposition001+
    type: VariantPathogenicityProposition
    subjectVariant: clinvar/208366+
    predicate: isCausalFor+
    objectCondition:+
      id: clinvar.trait/939+
      conceptType: Disease
      name: Autosomal dominant nonsyndromic hearing loss 2A+
      primaryCoding:+
        code: C2677637+
        system: https://www.ncbi.nlm.nih.gov/medgen/
        iris:
          - http://identifiers.org/medgen/C2677637
    penetranceQualifier:+
      primaryCoding:
        code: high
        system: ga4gh-gks-term:pathogenicity-penetrance-qualifier+
      name: high
  direction: supports+
  strength:+
    primaryCoding:
      code: definitive+
      system: ACMG Guidelines, 2015
  classification:+
    primaryCoding:
      code: pathogenic+
      system: ACMG Guidelines, 2015
  contributions:+
    - type: Contribution
      contributor:+
        id: clinvar.submitter/500139
        type: Agent
        name: ClinVar Staff, National Center for Biotechnology Information (NCBI)
      activityType: evaluated+
      date: '2015-08-20'+
    - type: Contribution
      contributor:
        id: clinvar.submitter/500139
        type: Agent
        name: ClinVar Staff, National Center for Biotechnology Information (NCBI)
      activityType: submitted
      date: '2018-06-12'
  specifiedBy:+
    type: Method
    reportedIn:+
      type: Document
      pmid: 25741868
      name: ACMG Guidelines, 2015