This element represents the interpretation of a variant according to the American College of Medical Genetics (ACMG) variant interpretation guidelines.
|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|
|variant||VariationDescriptor||1..1||a genetic/genomic variant|
|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|
|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.|
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"
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.
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.