VariantInterpretation¶
This element represents the interpretation of a variant according to the American College of Medical Genetics (ACMG) variant interpretation guidelines.
Data model¶
VariantInterpretation¶
Field | Type | Multiplicity | Description |
---|---|---|---|
acmg_pathogenicity_classification | AcmgPathogenicityClassification | 1..1 | one of the five ACMG pathogenicity categories, or NOT_PROVIDED. The default is NOT_PROVIDED |
therapeutic_actionability | TherapeuticActionability | 1..1 | The therapeutic actionability of the variant, default is UNKNOWN_ACTIONABILITY |
variation_descriptor | VariationDescriptor | 1..1 | a genetic/genomic variant |
AcmgPathogenicityClassification¶
Name | Ordinal | Description | |
---|---|---|---|
NOT_PROVIDED | 0 | The variant has not been subject to classification | |
BENIGN | 1 | This variant does not cause disease | |
LIKELY_BENIGN | 2 | This variant is not expected to have a major effect on disease. However | the scientific evidence is currently insufficient to prove this conclusively |
UNCERTAIN_SIGNIFICANCE | 3 | There is not enough information at this time to support a more definitive classification of this variant | |
LIKELY_PATHOGENIC | 4 | There is a high likelihood (greater than 90% certainty) that this variant is disease-causing | |
PATHOGENIC | 5 | This variant directly contributes to the development of disease |
TherapeuticActionability¶
Name | Ordinal | Description |
---|---|---|
UNKNOWN_ACTIONABILITY | 0 | There is not enough information at this time to support any therapeutic actionability for this variant |
NOT_ACTIONABLE | 1 | This variant has no therapeutic actionability. |
ACTIONABLE | 2 | This variant is known to be therapeutically actionable. |
Example¶
The following element shows how to denote an interpretation of a variant as pathogenic.
variantInterpretation:
acmgPathogenicityClassification: "PATHOGENIC"
variationDescriptor:
expressions:
- syntax: "hgvs"
value: "NM_001848.2:c.877G>A"
allelicState:
id: "GENO:0000135"
label: "heterozygous"
Explanations¶
acmg_pathogenicity_classification¶
The ACMG has recommended a five-tier classification system (Richards et al., 2015).
- Benign (BENIGN): This variant does not cause disease.
- Likely benign (LIKELY_BENIGN): This variant is not expected to have a major effect on disease; however, the scientific evidence is currently insufficient to prove this conclusively.
- Uncertain significance (UNCERTAIN_SIGNIFICANCE): There is not enough information at this time to support a more definitive classification of this variant.
- Likely pathogenic (LIKELY_PATHOGENIC): There is a high likelihood (greater than 90% certainty) that this variant is disease-causing.
- Pathogenic (PATHOGENIC): This variant directly contributes to the development of disease.
In the case that the variant has not been subject to classification, the value ‘NOT_PROVIDED’ MUST be used.
therapeutic_actionability¶
An enumeration flagging the variant as being a candidate for treatment/ clinical intervention of the disorder caused by this variant, which could improve the clinical outcome.
variation_descriptor¶
The subject of the variant interpretation. See VariationDescriptor for more information.