Observation-genetic - FHIR v3.0.2

FHIR Release 3 (STU)

This page is part of the FHIR Specification (v3.0.2: STU 3). The current version which supercedes this version is 5.0.0. For a full list of available versions, see the Directory of published versions . Page versions: R4 R3

10.1.14 Observation-genetics

(No assigned work group)

Maturity Level: N/A

Ballot Status: Informative

10.1.14.1 Overview

Observation-genetics-profile extends Observation resource to enable reporting of structured genetic test results. In addition, the genetics profile contextualizes well established standards from the field of clinical genetics into the standards of healthcare (e.g. HGNC - HUGO Gene Nomenclature Committee's international standard for gene names, symbols, and identifiers).

For use cases, details on how this resource interact with other Clinical Genomics resources or profiles, please refer to implementation guidance document here .

10.1.14.1.1 Genetic Standards and Resources include:

Variant Databases: dbSNP , ClinVar , and COSMIC
Reference Sequences: RefSeq and ENSEMBL
Gene Symbols and Identifiers: HGNC - Human Genee Nomenclature Committee
Variant Nomenclature: HGVS nomenclature from the Human Genome Variantion Society
Locus: Gene

10.1.14.2 Scope and Usage

The Observation-genetics profile supports reporting of a DNA variant at the genomic, cDNA, and protein change level. In addition, a condition context may be provided, as AssessedCondition. For large genomic tests, a condition may be used as an input into the analytic pipeline to aid in the identification of clinically relevant variants related to the test order. It is strongly encouraged to provide all available information in this profile for any reported variants, because receiving systems (e.g. discovery research, outcomes analysis, and public health reporting) may use this information to normalize variants over time or across sources. However, these data should not be used to dynamically correct/change variant representations for clinical use outside of the laboratory, due to insufficient information.

Implementers should be aware that semantic equivalency of results of genetic variants cannot be guaranteed unless there is an agreed upon standard between sending and receiving systems.

This FHIR genomics work is based on work of the HL7 Clinical Genomics Workgroup and modeled based on the Domain Analysis Model and SMART on FHIR Genomics as published in JAMIA 2015 (http://jamia.oxfordjournals.org/content/early/2015/07/21/jamia.ocv045.long).

The HL7 Clinical Genomics Work Group emphasizes the importance of transmitting structured genetic findings within the clinical, translational, and research environments fully integrated with other clinical data, in order to drive outcomes analysis, operational decision making, discovery research, and public health reporting. The standard doesn't currently cover the reporting of clinically relevant negative or wild type results within genetic data portion of the message.

Here is the document of HL7 Version 3 Domain Analysis Model where the examples used in genetics profile are from (Page 5).

10.1.14.3 Interpretation

Extension - geneticsInterpretation points to an Observation entity. In this Observation entity, Observation.component is used for recording clinical interpretations for variation.

Here is a LOINC panel that could be supported by Observation.component:

LOINC Codes
LOINC #	Component	Description/Comments
51963-7	Medication Assessed	A coded medication accessed in a pharmacogenetic test (recommend RxNorm).
51964-5	Drug Efficacy Analysis Overall Interpretation	Overall predicted phenotype for drug efficacy for all DNA Sequence Variations identified in a single case. LOINC Answer List values can be seen in table below.
51967-8	Genetic disease assessed	A coded disease which is associated with the region of DNA covered by the genetic test (recommend SNOMED).
51969-4	Genetic analysis summary report	Narrative report in disease diagnostic-based format, which is used for pharmacogenomic reporting as well and disease risk or diagnosis. These reports currently follow the same formatting recommendations.
51971-0	Drug metabolism analysis overall interpretation	Overall predicted phenotype for drug metabolism for all DNA Sequence Variations identified in a single case. LOINC Answer List values can be seen in table below.
53039-4	Genetic Disease Analysis Overall Carrier Interpretation	Carrier Identification interpretation of all identified DNA Sequence Variations along with any known clinical information for the benefit of aiding clinicians in understanding the results overall. LOINC Answer List values can be seen in table below.

LOINC Answer Lists
LOINC Code	Sequence	Answer text	LOINC answer code
51964-5	1	Responsive	LA6677-4
	2	Resistant	LA6676-6
	3	Negative	LA6577-6
	4	Inconclusive	LA9663-1
	5	Failure	LA9664-9
51971-0	1	Ultrarapid metabolizer	LA10315-2
	2	Extensive metabolizer	LA10316-0
	3	Intermediate metabolizer	LA10317-8
	4	Poor metabolizer	LA9657-3
	5	Inconclusive	LA9663-1
53039-4	1	Carrier	LA10314-5
	2	Negative	LA6577-6
	3	Inconclusive	LA9663-1
	4	Failure	LA9664-9

In addition, in this Observation entity, Observation.related is used to link itself with Observation-genetics profile. Observation.related.type is 'derived-from' as it provides clinical interpretation for variation recoreded in Observation-genetics entity.

10.1.14.4 Content

Profiles:
Observation-Genetics	Describes how the observation resource is used to report structured genetic test results
Extensions:
observation-geneticsDNASequenceVariantName	DNASequenceVariantName : Human Genome Variation Society (HGVS) nomenclature for a single or set of DNA Sequence Variation(s) identified in testing. The use of the nomenclature is also used to describe non-variations (aka. wild types). LOINC Code: (48004-6 ).
observation-geneticsDNAVariantId	DNAVariantId : Identifier for DNA sequence variant. If a germline variant, ClinVar or dbSNP identifier should be used. If a somatic variant, COSMIC identifier should be used, unless in ClinVar then either maybe used. Need to provide the code system used (ClinVar, dbSNP, COSMIC) LOINC Code: (48003-8 ).
observation-geneticsDNASequenceVariantType	DNASequenceVariantType : Codified type for associated DNA sequence variant. DNA sequence variants use the HGVS notation, which implies the DNA sequence variant type. LOINC Code: (48019-4 ).
observation-geneticsAminoAcidChangeName	AminoAcidChangeName : Human Genome Variation Society (HGVS) nomenclature for an amino acid change. Reference sequence ID used for HGVS naming must be annotated. An amino acid is a sequence feature that corresponds to a single amino acid residue in a polypeptide (SO:0001237 ). LOINC Code: (48005-3 ).
observation-geneticsAminoAcidChangeType	AminoAcidChangeType : Codified type for associated Amino Acid Change. LOINC Code: (48006-1 ).
observation-geneticsGene	Gene : A region (or regions) that includes all of the sequence elements necessary to encode a functional transcript. A gene may include regulatory regions, transcribed regions and/or other functional sequence regions (SO:0000704 ). This element is the official gene symbol approved by the HGNC, which is a short abbreviated form of the gene name (HGNC ). LOINC Code: (48018-6 ).
observation-geneticsDNARegionName	DNARegionName : A human readable name for the region of interest. Typically Exon #, Intron # or other. NOTE: This is not standardized and is mainly for convenience and display purposes. LOINC Code: (47999-8 ).
observation-geneticsAlleleName	AlleleName : An allele is one of a set of coexisting sequence variants of a gene (SO:0001023 ). This element is the common name for the allele. LOINC Code: (48008-7 ).
observation-geneticsAllelicState	AllelicState : The level of occurrence of a single DNA Sequence Variant within a set of chromosomes. Heterozygous indicates the DNA sequence variant is only present in one of the two genes contained in homologous chromosomes. Homozygous indicates the DNA Sequence Variant is present in both genes contained in homologous chromosomes. Hemizygous indicates the DNA Sequence Variant exists in the only single copy of a gene in a non-homologous chromosome (the male X and Y chromosome are non-homologous). Hemiplasmic indicates that the DNA Sequence Variant is present in some but not all of the copies of mitochondrial DNA. Homoplasmic indicates that the DNA Sequence Variant is present in all of the copies of mitochondrial DNA. LOINC Code: (53034-5 ).
observation-geneticsAllelicFrequency	AllelicFrequency : A physical quality which inheres to the allele by virtue of the number instances of the allele within a population. LOINC Code: (81258-6 ).
observation-geneticsCopyNumberEvent	CopyNumberEvent : A variation that increases or decreases the copy number of a given region (SO:0001019 ). Values: amplification/deletion/LOH.
observation-geneticsGenomicSourceClass	GenomicSourceClass : Source of sample used to determine the sequence in sequencing lab -- germline, somatic, prenatal. LOINC Code: (48002-0 ).
observation-geneticsPhaseSet	PhaseSet : Chromosomal phase set identifier (UUID/OID). All sequences with the same PhaseSet identifier are asserted to be on the same chromosome (cis).
observation-geneticsSequence	Sequence : Refers to the Sequence resource, representing raw genetics data.
observation-geneticsInterpretation	Interpretation : Clinical Interpretations for variant. It's a reference to an Observation resource.
Examples:
Genetics 1	Genetics example 1
Genetics 2	Genetics example 2
Genetics 3	Genetics example 3
Genetics 4	Genetics example 4
Genetics 5	Genetics example 5
Diplotype(with Haplotypes Ref)	Example of diplotype data (with haplotypes observation as reference)
Haplotype	Example of haplotype data that is basis of a diplotype data
Haplotype-2	Example of another haplotype data that is basis of a diplotype data
Phenotype	Example of phenotype data
TPMT-diplotype	Example of a TPMT diplotype that link to two TPMT haplotype observations
TPMT-haplotype-one	Example of a TPMT haplotype observation
TPMT-haplotype-two	Example of another TPMT haplotype observation

10.1.14.5 Search Parameters

Search parameters defined by this package. See Searching for more information about searching in REST, messaging, and services.

Name	Type	Description	Paths	Source
amino-acid-change	string	HGVS Protein Change		XML / JSON
dna-variant	string	HGVS DNA variant		XML / JSON
gene-amino-acid-change	string	HGNC gene symbol and HGVS Protein change		XML / JSON
gene-dnavariant	string	HGNC gene symbol and HGVS DNA Variant		XML / JSON
gene-identifier	token	HGNC gene symbol and identifier		XML / JSON