Function Constraint

Definition and Information Model

Warning

This data class is at a draft maturity level and may change significantly in future releases. Maturity levels are described in the GKS Maturity Model.

Computational Definition

A classification of the protein functional consequence that characterizes members of this categorical variant.

Information Model

Some FunctionConstraint attributes are inherited from Constraint.

Field	Type	Limits	Description
type	string	1..1	MUST be “FunctionConstraint”
functionConsequence	MappableConcept	1..1	The functional consequence of members of this categorical variant, as defined by an external ontology. We recommend using one of the defined terms from The Sequence Ontology. See Implementation Guidance for more details.
description	string	0..1	A free-text description of the function change.

Examples

The following example Categorical Variants utilize this Constraint:

A representative example of this Constraint, from NRAS functionally normal variants:

    },
    {
      "type": "FunctionConstraint",
      "functionConsequence": {
        "type": "MappableConcept",
        "id": "SO:0002219",
        "name": "functionally normal",
        "primaryCoding": {
          "id": "SO:0002219",
          "name": "functionally_normal",
          "system": "http://www.sequenceontology.org",
          "code": "SO:0002219",
          "iris": [
            "http://www.sequenceontology.org/browser/current_release/term/SO:0002219"
          ]
        }
      },

Implementation Guidance

This Constraint is used in two circumstances:

To define a Canonical Allele, Categorical Copy Number Variant, Gene Fusion, or Protein Sequence Consequence Categorical Variant with a known functional impact.

Note

If your implementation also uses the Variant Annotation Specification, consider associating the Categorical Variant with a Genomic Knowledge Statement based on an Experimental Variant Functional Impact.
When broadly defining a Categorical Variant that can be satisfied by many possible variants, as long as they are described using this Constraint and the same associated definition. For example, BRCA2 loss of function variants, as shown in the Examples.

functionConsequence

The functionConsequence attribute is required and is a MappableConcept, meaning that it should be represented using a term from an externally defined ontology. We recommend using descendant terms of the functional effect variant concept in the Sequence Ontology, such as:

Name	Code	SO Definition	SO Name
dominant negative variant	SO:0002052	A variant where the mutated gene product adversely affects the other (wild type) gene product.	dominant_negative_variant
gain of function	SO:0002053	A sequence variant whereby new or enhanced function is conferred on the gene product.	gain_of_function_variant
loss of function	SO:0002054	A sequence variant whereby the gene product has diminished or abolished function.	loss_of_function_variant
loss of heterozygosity	SO:0001786	A functional variant whereby the sequence alteration causes a loss of function of one allele of a gene.	loss_of_heterozygosity
functionally normal	SO:0002219	A sequence variant in which the function of a gene product is retained with respect to a reference.	functionally_normal