Custom Variant Pathogenicity Statement Example

Building Custom Statement Models:

• Representation of a particular type of Statement or Evidence Line using the VA-Spec does not always require a Profile to be specifically defined for it.

• The Statement and Evidence Line Community Profiles included in version 1.0 of the VA-Spec are there to support data providers pursuing strict alignment with a particular community guidelines.

• Implementers who do not seek such alignment can build their own schema for Statements or Evidence Lines to report on any of the knowledge types specified in VA Base Proposition profiles.

• For example, starting with the core Statement<Statement> class, simply bind its proposition attribute to the relevant Proposition base profile, and the permissive core Statement attributes will not impose community-specific constraints around representation of additional information about the Statement (e.g. strength, provenance, source documents, etc).

Example Description:

• The example below represents the same ClinVar-based Variant Pathogenicity Statement as in this Simple Test Fixtures Example, but does not conform to the ACMG 2015 Community Profile for this statement type.

• Instead, the schema uses the core Statement class with in a base Variant Pathogenicity Proposition, and the looser constraints on the core class to allow use of the implementers preferred vocabularies for capturing things like Statement strength and classification.

• Annotations in the example point out where the implementers preferred codes are used instead of ACMG-based terms.

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: established+
      system: Implementer System 1
  classification:+
    primaryCoding:
      code: disease-causing+
      system: ACMG Guidelines, 2015
  contributions:+
    - type: Contribution
      contributor:+
        id: clinvar.submitter/500139
        type: Agent
        name: ClinVar Staff, National Center for Biotechnology Information (NCBI)
      activityType:+
        name: evaluated
      date: '2015-08-20'+
    - type: Contribution
      contributor:
        id: clinvar.submitter/500139
        type: Agent
        name: ClinVar Staff, National Center for Biotechnology Information (NCBI)
      activityType:
        name: submitted
      date: '2018-06-12'
  specifiedBy:+
    type: Method
    reportedIn:+
      type: Document
      name: Alternate Guidelines and Terminology for Variant Pathogenicity Classification