VariantInterpretation

This element represents the interpretation of a variant according to the American College of Medical Genetics (ACMG) variant interpretation guidelines.

Data model

VariantInterpretation

Definition of the `VariantInterpretation` element
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

Definition of the `AcmgPathogenicityClassification` enumeration
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

Definition of the `TherapeuticActionability` enumeration
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.