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CNV Annotation Formats

ISCN

Sine 1963, the International System for Human Cytogenetic Nomenclature (ISCN) has provided standards and guidelines for annotation of human karyotypes and cytogenetic abnormalities.

Recent editions have tried to accomodate for genomic variants derived from molecular and molecular-cytogenetics technologies such as FISH, genomic microarrays and DNA sequencing.

Examples (CNV)

  • 46,XX,trp(8)(q21q24)
  • ish cgh dim(17p12p11),enh(8)(q24)
    • chromosomal Comparativ Genomic Hybridization (CGH)
  • ISCN 2016 is the latest edition, available as book (Karger)

HGVS

VCF

While VCF is a file format, originally developed (and optimised) for the representation of possibly recurring variants across a set of analyses, it also allows for the storage & representation of CNV events.

Variant Schemas

GA4GH "Variant Representation" schema

The "Genomic Knowledge Standards" (GKS) of the Global Alliance for Genomics and Health GA4GH develops a modern schema for the unambiguous representation, transmission and recovery of sequence variants (genomic and beyond).

The first release of the [GA4GH Variation Representation Specification (vr-spec v1.0) does not yet include the option to represent structural variants. However, the internal roadmap of the project points towards an extension for CNV representation in 2020.

Ad-Hoc & "Community" Formats

Progenetix Variant schema

The Progenetix cancer genomics resource store their millions of CNVs in as data objects in MongoDB document databases. The format of the single variants is based on the original GA4GH schema (see above), with some extensions and modifications.

Development of the Progenetix format closely follows the work of the GA4GH GKS group adopts core objects and concepts from vr-spec repository.

The Progenetix data serves as the repository behind the Beacon+ forward looking implementation of the ELIXIR Beacon project.

Progenetix CNV example

{
  _id: ObjectId("5bab576a727983b2e00b8d32"),
  id: 'pgxvar-5bab576a727983b2e00b8d32',
  variant_internal_id: '11:52900000-134452384:DEL',
  callset_id: 'pgxcs-kftvldsu',
  biosample_id: 'pgxbs-kftva59y',
  individual_id: 'pgxind-kftx25eh',
  variant_state: { id: 'EFO:0030067', label: 'copy number loss' },
  type: 'RelativeCopyNumber',
  location: {
    sequence_id: 'refseq:NC_000011.10',
    type: 'SequenceLocation',
    interval: {
      start: { type: 'Number', value: 52900000 },
      end: { type: 'Number', value: 134452384 }
    }
  },
  relative_copy_class: 'partial loss',
  updated: '2022-03-29T14:36:47.454674'
}