Function Variant
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 representation of the constraints for matching knowledge about function variants; e.g., gain-of-function or loss-of-function.
Information Model
The FunctionVariant is a Categorical Variant with at least two constraints:
Examples
The following are example implementations of that satisfy the FunctionVariant recipe:
NRAS functionally normal variants
{
"$schema": "https://json-schema.org/draft/2020-12/schema",
"$id": "https://w3id.org/ga4gh/schema/cat-vrs/1.0.0/json/example_functionVariant-ex1",
"title": "example_functionVariant-ex1",
"type": "CategoricalVariant",
"id": "civic.mpid:4428",
"name": "NRAS functionally normal variants",
"description": "An example categorical variant that uses FeatureContextConstraint and FunctionConstraint.",
"constraints": [
{
"type": "FeatureContextConstraint",
"featureContext": {
"id": "hgnc:7989",
"conceptType": "Gene",
"name": "NRAS",
"primaryCoding": {
"id": "hgnc:7989",
"name": "NRAS",
"system": "https://www.genenames.org",
"code": "HGNC:7989",
"iris": [
"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7989"
]
}
}
},
{
"type": "FunctionConstraint",
"functionConsequence": {
"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"
]
}
},
"description": "Function consequence described as functionally normal using Sequence Ontology."
}
],
"members": [
{
"id": "ga4gh:VA.GSV_U1hzMrHMWEMEqj-22KMJ9KBjzg3G",
"type": "Allele",
"name": "NM_002524.5:c.170A>C",
"description": "VRS variation of NM_002524.5(NRAS):c.170A>C(p.D57A), generated with the VICC Variation Normalizer (https://github.com/cancervariants/variation-normalization).",
"digest": "GSV_U1hzMrHMWEMEqj-22KMJ9KBjzg3G",
"expressions": [
{
"syntax": "hgvs.c",
"value": "NM_002524.5:c.170A>C"
}
],
"location": {
"id": "ga4gh:SL.giseM38uWBFp7prflNpHkr6HP_8xsCdj",
"description": "Coding DNA (cDNA) position 170 of the NRAS MANE Select coding transcript (refseq:NM_002524.5), corresponding to genomic position 114713920 on chromosome 1 (refseq:NC_000001.11, GRCh38).",
"extensions": [
{
"name": "GRCh38, 1-based, genomic position",
"value": "chr1:114713920",
"description": "Genomic position 114,713,920 on chromosome 1 (refseq:NC_000001.11, GRCh38)."
},
{
"name": "GRCh38, 1-based, inclusive interval notation",
"value": "chr1:114713920-114713920",
"description": "Genomic position 114,713,920 to 114,713,920 on chromosome 1 (refseq:NC_000001.11, GRCh38)."
},
{
"name": "GRCh38, 0-based, half-open interval notation",
"value": "chr1:114713919-114713920",
"description": "Genomic position 114,713,919 to 114,713,920 on chromosome 1 (refseq:NC_000001.11, GRCh38)."
}
],
"type": "SequenceLocation",
"digest": "giseM38uWBFp7prflNpHkr6HP_8xsCdj",
"sequenceReference": {
"id": "refseq:NM_002524.5",
"name": "NM_002524.5",
"description": "The MANE Select (GRCh38) coding transcript for NRAS.",
"aliases": [
"ensembl:ENST00000369535.5",
"ga4gh:SQ.sMBMPz32WlhQGTxBagnyMCUdy2OD2M--"
],
"type": "SequenceReference",
"refgetAccession": "SQ.sMBMPz32WlhQGTxBagnyMCUdy2OD2M--",
"residueAlphabet": "na"
},
"start": 300,
"end": 301,
"sequence": "A"
},
"state": {
"type": "LiteralSequenceExpression",
"sequence": "C"
}
}
],
"maturity": "draft"
}
BRCA2 loss of function variants
{
"$schema": "https://json-schema.org/draft/2020-12/schema",
"$id": "https://w3id.org/ga4gh/schema/cat-vrs/1.0.0/json/example_functionVariant-ex2",
"title": "example_functionVariant-ex2",
"type": "CategoricalVariant",
"id": "civic.mpid:186",
"name": "BRCA2 loss of function variants",
"description": "An example categorical variant that uses FeatureContextConstraint and FunctionConstraint.",
"constraints": [
{
"type": "FeatureContextConstraint",
"featureContext": {
"id": "hgnc:1101",
"conceptType": "Gene",
"name": "BRCA2",
"primaryCoding": {
"id": "hgnc:1101",
"name": "BRCA2",
"system": "https://www.genenames.org",
"code": "HGNC:1101",
"iris": [
"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1101"
]
}
}
},
{
"type": "FunctionConstraint",
"functionConsequence": {
"id": "SO:0002054",
"name": "loss of function",
"primaryCoding": {
"id": "SO:0002054",
"name": "loss_of_function_variant",
"system": "http://www.sequenceontology.org",
"code": "SO:0002054",
"iris": [
"http://www.sequenceontology.org/browser/current_release/term/SO:0002054"
]
}
},
"description": "Function consequence described as loss of function using Sequence Ontology."
}
],
"maturity": "draft"
}
PIK3CA p.R38H
{
"$schema": "https://json-schema.org/draft/2020-12/schema",
"$id": "https://w3id.org/ga4gh/schema/cat-vrs/1.0.0/json/example_functionVariant-ex3",
"title": "example_functionVariant-ex3",
"type": "CategoricalVariant",
"id": "civic.mpid:1150",
"name": "PIK3CA p.R38H",
"description": "An example categorical variant that uses DefiningAlleleConstraint, FeatureContextConstraint, and FunctionConstraint.",
"constraints": [
{
"type": "DefiningAlleleConstraint",
"allele": {
"id": "ga4gh:VA.gFYUMkeAme8HeNqcBIDPYIB45_xRa9Qi",
"type": "Allele",
"name": "NM_006218.4:c.113G>A",
"description": "VRS Variation of NM_006218.4:c.113G>A, generated with the VICC Variation Normalizer (https://github.com/cancervariants/variation-normalization).",
"digest": "gFYUMkeAme8HeNqcBIDPYIB45_xRa9Qi",
"expressions": [
{
"syntax": "hgvs.c",
"value": "NM_006218.4:c.113G>A"
}
],
"location": {
"id": "ga4gh:SL.rZhFJCEGRkU-G3EqaGuUpefj2bP94NLi",
"description": "Coding DNA (cDNA) position 113 of the PIK3CA MANE Select coding transcript (refseq:NM_006218.4), corresponding to genomic position 179198938 on chromosome 3 (refseq:NC_000003.12, GRCh38).",
"extensions": [
{
"name": "GRCh38, 1-based, genomic position",
"value": "chr3:179198938",
"description": "Genomic position 179,198,938 on chromosome 3 (refseq:NC_000003.12, GRCh38)."
},
{
"name": "GRCh38, 1-based, inclusive interval notation",
"value": "chr3:179198938-179198938",
"description": "Genomic positions 179,198,938 to 179,198,938 on chromosome 3 (refseq:NC_000003.12, GRCh38)."
},
{
"name": "GRCh38, 0-based, half-open interval notation",
"value": "chr3:179198937-179198938",
"description": "Genomic positions 179,198,937 to 179,198,938 on chromosome 3 (refseq:NC_000003.12, GRCh38)."
}
],
"type": "SequenceLocation",
"digest": "rZhFJCEGRkU-G3EqaGuUpefj2bP94NLi",
"sequenceReference": {
"id": "refseq:NM_006218.4",
"name": "NM_006218.4",
"description": "The MANE Select (GRCh38) coding transcript for PIK3CA.",
"aliases": [
"ensembl:ENST00000263967.4",
"ga4gh:SQ.vV37R3hERpo6hA6RBsi9AaaMoY7ELvk9"
],
"type": "SequenceReference",
"refgetAccession": "SQ.vV37R3hERpo6hA6RBsi9AaaMoY7ELvk9",
"residueAlphabet": "na"
},
"start": 435,
"end": 436,
"sequence": "G"
},
"state": {
"type": "LiteralSequenceExpression",
"sequence": "A"
}
}
},
{
"type": "FeatureContextConstraint",
"featureContext": {
"id": "hgnc:8975",
"conceptType": "Gene",
"name": "PIK3CA",
"primaryCoding": {
"id": "hgnc:8975",
"system": "https://www.genenames.org",
"code": "HGNC:8975",
"iris": [
"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:8975"
]
}
}
},
{
"type": "FunctionConstraint",
"functionConsequence": {
"id": "SO:0002053",
"name": "gain of function",
"primaryCoding": {
"id": "SO:0002053",
"name": "gain_of_function",
"system": "http://www.sequenceontology.org",
"code": "SO:0002053",
"iris": [
"http://www.sequenceontology.org/browser/current_release/term/SO:0002053"
]
}
},
"description": "Function consequence described as gain of function using Sequence Ontology."
}
],
"members": [
{
"id": "ga4gh:VA.gFYUMkeAme8HeNqcBIDPYIB45_xRa9Qi",
"type": "Allele",
"name": "NM_006218.4:c.113G>A",
"description": "VRS Variation of NM_006218.4:c.113G>A, generated with the VICC Variation Normalizer (https://github.com/cancervariants/variation-normalization).",
"digest": "gFYUMkeAme8HeNqcBIDPYIB45_xRa9Qi",
"expressions": [
{
"syntax": "hgvs.c",
"value": "NM_006218.4:c.113G>A"
}
],
"location": {
"id": "ga4gh:SL.rZhFJCEGRkU-G3EqaGuUpefj2bP94NLi",
"description": "Coding DNA (cDNA) position 113 of the PIK3CA MANE Select coding transcript (refseq:NM_006218.4), corresponding to genomic position 179198938 on chromosome 3 (refseq:NC_000003.12, GRCh38).",
"extensions": [
{
"name": "GRCh38, 1-based, genomic position",
"value": "chr3:179198938",
"description": "Genomic position 179,198,938 on chromosome 3 (refseq:NC_000003.12, GRCh38)."
},
{
"name": "GRCh38, 1-based, inclusive interval notation",
"value": "chr3:179198938-179198938",
"description": "Genomic positions 179,198,938 to 179,198,938 on chromosome 3 (refseq:NC_000003.12, GRCh38)."
},
{
"name": "GRCh38, 0-based, half-open interval notation",
"value": "chr3:179198937-179198938",
"description": "Genomic positions 179,198,937 to 179,198,938 on chromosome 3 (refseq:NC_000003.12, GRCh38)."
}
],
"type": "SequenceLocation",
"digest": "rZhFJCEGRkU-G3EqaGuUpefj2bP94NLi",
"sequenceReference": {
"id": "refseq:NM_006218.4",
"name": "NM_006218.4",
"description": "The MANE Select (GRCh38) coding transcript for PIK3CA.",
"aliases": [
"ensembl:ENST00000263967.4",
"ga4gh:SQ.vV37R3hERpo6hA6RBsi9AaaMoY7ELvk9"
],
"type": "SequenceReference",
"refgetAccession": "SQ.vV37R3hERpo6hA6RBsi9AaaMoY7ELvk9",
"residueAlphabet": "na"
},
"start": 435,
"end": 436,
"sequence": "G"
},
"state": {
"type": "LiteralSequenceExpression",
"sequence": "A"
}
}
],
"maturity": "draft"
}