ARCHETYPE Genomic variant result (openEHR-EHR-CLUSTER.genomic_variant_result.v1)

ARCHETYPE IDopenEHR-EHR-CLUSTER.genomic_variant_result.v1
ConceptGenomic variant result
DescriptionFindings and annotations related to one variant found in a human individual by a sequencing test.
UseUse to report findings and annotations related to one variant found in the genome by a sequencing test. This archetype has been designed to be nested in the 'Test result' SLOT within the OBSERVATION.laboratory_test_result archetype. It is intended to provide a consistent framework for nesting any specific genomic variant CLUSTER archetype within the 'Structured variant' SLOT. The archetype may also contain some key information about the methodology, i.e., the reference genome assembly and the bioinformatics pipeline used, to ensure proper interpretability and consistency of the results. However, when more details about the test method are to be reported, this archetype should be used in conjunction with the archetype openEHR-EHR-CLUSTER.sequencing_assay.v0. In that case, it is recommended to report all information about the method used, using the sequencing assay, and be cautious not to duplicate the information. This archetype allows the recording of genomic variants in both the HGVS syntax in an inline parsable element, and an atomic, structured form through the use of a nested CLUSTER archetype for specific variant types. If both of those representations are used simultaneously, they need to represent identical data. Note that in the case of a multiallelic variant, it is required to instantiate the archetype as many times as the number of alternative alleles whose data are to be reported for that position in the genome.
MisuseNot to be used for recording information about the comparison of several samples. Use a specific archetype for this purpose.
PurposeTo report findings and annotations related to one variant found in the genome by a sequencing test.
Referencesden Dunnen JT, Dalgleish R, Maglott DR, Hart RK, Greenblatt MS, McGowan-Jordan J, Roux AF, Smith T, Antonarakis SE, Taschner PE. HGVS Recommendations for the Description of Sequence Variants: 2016 Update. Hum Mutat. 2016 Jun;37(6):564-9. doi: 10.1002/humu.22981. Epub 2016 Mar 25. PubMed PMID: 26931183. Sequence variants available from: https://varnomen.hgvs.org/.

HL7 FHIR R4 [Internet]. HL7 International; 2018. Genomic Implementation Guidance; 2018 [cited 2019 05 23]. Available from: https://www.hl7.org/fhir/genomics.html.

Rehm HL, Bale SJ, Bayrak-Toydemir P, Berg JS, Brown KK, Deignan JL, Friez MJ, Funke BH, Hegde MR, Lyon E. ACMG clinical laboratory standards for next-generation sequencing. Genet Med. 2013 Sep;15(9):733-47. doi: 10.1038/gim.2013.92. Epub 2013 Jul 25. PubMed PMID: 23887774; PubMed Central PMCID: PMC4098820.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5. PubMed PMID: 25741868; PubMed Central PMCID: PMC4544753.
Copyright© openEHR Foundation
AuthorsAuthor name: Cecilia Mascia
Organisation: CRS4, Italy
Email: cecilia.mascia@crs4.it
Date originally authored: 2019-01-15
Other Details LanguageAuthor name: Cecilia Mascia
Organisation: CRS4, Italy
Email: cecilia.mascia@crs4.it
Date originally authored: 2019-01-15
Other Details (Language Independent)
  • Licence: This work is licensed under the Creative Commons Attribution-ShareAlike 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-sa/4.0/.
  • Custodian Organisation: openEHR Foundation
  • References: den Dunnen JT, Dalgleish R, Maglott DR, Hart RK, Greenblatt MS, McGowan-Jordan J, Roux AF, Smith T, Antonarakis SE, Taschner PE. HGVS Recommendations for the Description of Sequence Variants: 2016 Update. Hum Mutat. 2016 Jun;37(6):564-9. doi: 10.1002/humu.22981. Epub 2016 Mar 25. PubMed PMID: 26931183. Sequence variants available from: https://varnomen.hgvs.org/. HL7 FHIR R4 [Internet]. HL7 International; 2018. Genomic Implementation Guidance; 2018 [cited 2019 05 23]. Available from: https://www.hl7.org/fhir/genomics.html. Rehm HL, Bale SJ, Bayrak-Toydemir P, Berg JS, Brown KK, Deignan JL, Friez MJ, Funke BH, Hegde MR, Lyon E. ACMG clinical laboratory standards for next-generation sequencing. Genet Med. 2013 Sep;15(9):733-47. doi: 10.1038/gim.2013.92. Epub 2013 Jul 25. PubMed PMID: 23887774; PubMed Central PMCID: PMC4098820. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5. PubMed PMID: 25741868; PubMed Central PMCID: PMC4544753.
  • Original Namespace: org.openehr
  • Custodian Namespace: org.openehr
  • Original Publisher: openEHR Foundation
  • MD5-CAM-1.0.1: 8BA808D426A0B37C7CF80876149FF609
  • Build Uid: 13271728-1155-4b60-adfe-898df1e4dc70
  • Revision: 1.1.0
Keywordsvariation, VCF, variant, genetic, genomic, variant calling, sequence, mutation, allele, genotype
Lifecyclepublished
UIDddb13dc5-5227-48f7-93f5-1b6825ace295
Language useden
Citeable Identifier1246.145.399
Revision Number1.1.0
items
Bioinformatic analysis workflowBioinformatic analysis workflow: Structured details about the bioinformatic analysis workflow or the protocol that is used.
Include:
openEHR-EHR-CLUSTER.knowledge_base_reference.v1 and specialisations or
openEHR-EHR-CLUSTER.device.v1 and specialisations
Reference genomeReference genome: Structured details about the specific version of the human sequence assembly used for annotation.
For example: 'GCF_000001405.38'. Source name: 'NCBI'. Accession number: 'GCF_000001405'. Version number: 'GCF_000001405.38'. URL: 'https://www.ncbi.nlm.nih.gov/assembly/GCF_000001405.38/'.
Include:
openEHR-EHR-CLUSTER.reference_sequence.v1 and specialisations
Variant identificationVariant identification: A reference to a specific variation recorded into an external biological variation database.
For example: 'rs123456' (Item name) from 'dbSNP' (Knowledge base name) 'version 151' (Knowledge base version). This CLUSTER.knowledge_base_reference archetype is repeatable to allow several different IDs from different databases for the same variant.
Include:
openEHR-EHR-CLUSTER.knowledge_base_reference.v1 and specialisations
VariantVariant: Description of the variation at the genomic level following the HGVS nomenclature.
For example: 'g.33038255C>A'. If both this element and the 'Structured variant' SLOT are used simultaneously, they need to represent identical data.
Structured variantStructured variant: Structured description of the genomic variant.
This element is set to multiple occurrence to allow templates to be built with several different variant types allowed. However, when storing data, there should never be more than one CLUSTER archetype inserted here. If both this SLOT and the 'Variant' data element are used simultaneously, they need to represent identical data.
Include:
openEHR-EHR-CLUSTER.genomic_deletion_insertion_variant.v1 and specialisations or
openEHR-EHR-CLUSTER.genomic_duplication_variant.v1 and specialisations or
openEHR-EHR-CLUSTER.genomic_inversion_variant.v1 and specialisations or
openEHR-EHR-CLUSTER.genomic_insertion_variant.v1 and specialisations or
openEHR-EHR-CLUSTER.genomic_conversion_variant.v1 and specialisations or
openEHR-EHR-CLUSTER.genomic_substitution_variant.v1 and specialisations or
openEHR-EHR-CLUSTER.genomic_copy_number_variant.v1 and specialisations or
openEHR-EHR-CLUSTER.genomic_repeated_sequence_variant.v1 and specialisations or
openEHR-EHR-CLUSTER.genomic_deletion_variant.v1 and specialisations
TranscriptTranscript: Structured details about the transcript which is potentially affected by the variant.
Transcript reference sequenceTranscript reference sequence: Structured details about the transcribed reference sequence.
For example: Source name: 'NCBI'. Accession number: 'NM_015557'. Version number: 'NM_015557.2'. URL: 'https://www.ncbi.nlm.nih.gov/nuccore/304361774'.
Include:
openEHR-EHR-CLUSTER.reference_sequence.v1 and specialisations
DNA region nameDNA region name: The human readable name for the region of interest.
For example: 'exon number', 'intron number', 'splice site' or other.
Distance from splicing siteDistance from splicing site: Distance in nucleotides between mutation and exon–intron junction.
DNA changeDNA change: Description of the variation at the DNA level following the HGVS nomenclature.
For example: 'c.5249C>T'.
Amino acid changeAmino acid change: Description of the variation at the protein level following the HGVS nomenclature.
For example: 'p.T1750M'.
Amino acid change typeAmino acid change type: Codified type for associated amino acid marker.
Choice of:
  •  Coded Text
    • Wild type [The sequence at a given position is identical to the reference sequence.]
      [LOINC(2.65)::LA9658-1 | Wild type]
    • Deletion [A deletion in the amino acid sequence.]
      [LOINC(2.65)::LA6692-3 | Deletion]
    • Duplication [A duplication in the amino acid sequence.]
      [LOINC(2.65)::LA6686-5 | Duplication]
    • Frameshift [A frameshift in the amino acid sequence.]
      [LOINC(2.65)::LA6694-9 | Frameshift]
    • Initiating methionine [A variant in a sequence affecting the translation initiation codon.]
      [LOINC(2.65)::LA6695-6 | Initiating Methionine]
    • Insertion [An insertion in the amino acid sequence.]
      [LOINC(2.65)::LA6687-3 | Insertion]
    • Insertion and deletion [An insertion/deletion in the amino acid sequence.]
      [LOINC(2.65)::LA9659-9 | Insertion and Deletion]
    • Missense [One amino acid is replaced by another amino acid.]
      [LOINC(2.65)::LA6698-0 | Missense]
    • Nonsense [An amino acid is replaced by a translational stop codon (termination codon).]
      [LOINC(2.65)::LA6699-8 | Nonsense]
    • Silent [A variant in a DNA sequence that does not change the amino acid sequence of the encoded protein.]
      [LOINC(2.65)::LA6700-4 | Silent]
    • Stop codon mutation [A variant in a sequence affecting the translational stop codon.]
      [LOINC(2.65)::LA6701-2 | Stop Codon Mutation]
  •  Text
RNA changeRNA change: Description of the variation at the RNA level following the HGVS nomenclature.
For example: 'r.76a>u'.
Predicted impactPredicted impact: Estimate of the effects that the variant may have on the transcript.
Predicted impact knowledge basePredicted impact knowledge base: Structured details about the reference used to calculate the predicted impact.
For example 'CADD', 'SIFT', etc.
Include:
openEHR-EHR-CLUSTER.knowledge_base_reference.v1 and specialisations or
openEHR-EHR-CLUSTER.device.v1 and specialisations
ScoreScore: The calculated value.
For example: '30.2'.
Property: Qualified real
Units:
Qualitative predictionQualitative prediction: Human readable version of the predicted impact.
For example: 'probably damaging'.
Functional impactFunctional impact: Interpretation of the variation linked to a specific paper.
ImpactImpact: Single word or phrase describing the reported impact of the specific variant.
For example: 'activating', 'deactivating', 'dysfunction', 'gain of function'. Coding with a terminology is preferred, where possible.
SourceSource: The reference to the specific research paper.
Include:
openEHR-EHR-CLUSTER.citation.v0 and specialisations
GeneGene: Structured details about the gene carrying the variant.
Gene symbolGene symbol: The official gene symbol approved by the HGNC, which is a short abbreviated form of the gene name.
For example 'CHD5'.
Gene nameGene name: The full gene name approved by the HGNC that conveys the character or function of the gene.
For example 'Chromodomain helicase DNA binding protein 5'.
Copy number overlapCopy number overlap: The fraction of gene region covered by copy number.
Part of fusionPart of fusion: States if the gene is part of a fusion gene and if it is the first or second part of the fusion gene.
  • First [First part of a fusion gene.]
  • Second [Second part of a fusion gene.]
ACMG classificationACMG classification: The clinical significance according to the ACMG recommendations.
  • Pathogenic [Pathogenic variant.]
    [LOINC(2.65)::LA6668-3 | Pathogenic]
  • Likely pathogenic [Likely pathogenic variant.]
    [LOINC(2.65)::LA26332-9 | Likely pathogenic]
  • Uncertain significance [Variant of uncertain significance.]
    [LOINC(2.65)::LA26333-7 | Uncertain significance]
  • Likely benign [Likely benign variant.]
    [LOINC(2.65)::LA26334-5 | Likely benign]
  • Benign [Benign variant.]
    [LOINC(2.65)::LA6675-8 | Benign]
Fusion exonFusion exon: The number of the exon which is part of the fusion.
min: >0

Best transcript candidateBest transcript candidate: The ID of the transcript with the highest predicted impact.
For example: 'ENST00000413998.7'.
ConservationConservation: Structured details about the evolutionary conservation.
Conservation score knowledge baseConservation score knowledge base: Structured details about the reference used to calculate the conservation score.
For example 'PhastCons7-way'.
Include:
openEHR-EHR-CLUSTER.knowledge_base_reference.v1 and specialisations or
openEHR-EHR-CLUSTER.device.v1 and specialisations
ScoreScore: The conservation score.
Property: Qualified real
Units:
Read depthRead depth: The total number of reads mapped at this specific location.
min: >=0

Allele depthAllele depth: The number of reads that support the reported variant.
min: >=0

Allele frequencyAllele frequency: The relative frequency of an allele at a particular locus.
For example: '0.63'.
Property: Qualified real
Units: 0.0..1.0
Population allele frequency detailsPopulation allele frequency details: The relative frequency of a particular allele in the population.
Population allele frequency knowledge basePopulation allele frequency knowledge base: Structured details about the database used to calculate the allele frequency.
Include:
openEHR-EHR-CLUSTER.knowledge_base_reference.v1 and specialisations or
openEHR-EHR-CLUSTER.device.v1 and specialisations
Population allele frequencyPopulation allele frequency: The population allele frequency.
For example: '0.43'.
Property: Qualified real
Units: 0.0..1.0
VCF quality filterVCF quality filter: Structured details about the quality filters that have been applied to the data.
This field is derived from the FILTER column of VCF.
Filter nameFilter name: Name of the quality filter.
For example: 'q10'.
DescriptionDescription: Quality filter extended description.
For example: 'at this site the quality is below 10'.
Filter passedFilter passed: Did the variant pass the quality filter?
Record as 'True' if the filter was passed.
Strand bias ratioStrand bias ratio: The ratio of the strand bias.
Property: Qualified real
Units:
Strand bias p-valueStrand bias p-value: The Phred-scaled p-value of the strand bias.
Property: Qualified real
Units:
GenotypeGenotype: Genotype encoded as allele values.
The format for the genotype should be value separated by either of / or | (0 for the reference allele, 1 for the first alternate, etc.). For example: '1 | 0' or '0/0/1'.
Allelic stateAllelic state: The level of occurrence of a single DNA marker within a set of chromosomes.
This is the human readable version of genotype, e.g.: 'Heterozygous', 'Homozygous'.
Choice of:
  •  Coded Text
    • Heteroplasmic [Heteroplasmic.]
      [LOINC(2.65)::LA6703-8 | Heteroplasmic]
    • Homoplasmic [Homoplasmic.]
      [LOINC(2.65)::LA6704-6 | Homoplasmic]
    • Homozygous [Homozygous.]
      [LOINC(2.65)::LA6705-3 | Homozygous]
    • Heterozygous [Heterozygous.]
      [LOINC(2.65)::LA6706-1 | Heterozygous]
    • Hemizygous [Hemizygous.]
      [LOINC(2.65)::LA6707-9 | Hemizygous]
  •  Text
Genotype qualityGenotype quality: Conditional genotype quality, encoded as a Phred quality.
min: >=0

Genotype probabilityGenotype probability: A comma separated list of the log10-scaled genotype likelihoods for all possible genotypes, given the reference and the alternate alleles.
Specimen identifierSpecimen identifier: Identification of the specimen used for the genomic result.
In some situations, a single OBSERVATION.laboratory_test_result archetype will contain multiple CLUSTER.specimen archetypes and multiple CLUSTER.genomic_variant_result archetypes. In these situations, this 'Specimen identifier' data element is needed to be able to connect the results with the correct specimens.
Choice of:
  •  Identifier
  •  URI
Additional detailsAdditional details: Additional details to be captured.
For example, there may be a need to attach a file that contains a representation of the variant description in different recognised format, such as GA4GH VRS or HL7 FHIR. In such cases, the archetype openEHR-EHR-CLUSTER.media_file.v1, or other relevant one, can be included in this slot for this purpose.
Include:
All not explicitly excluded archetypes
Other contributorsVebjørn Arntzen, Oslo University Hospital, Norway (openEHR Editor)
Silje Ljosland Bakke, Helse Vest IKT AS, Norway (openEHR Editor)
SB Bhattacharyya, Sudisa Consultancy Services, India
Shahla Foozonkhah, Iran ministry of health and education, Iran
Francesca Frexia, CRS4 - Center for advanced studies, research and development in Sardinia, Italy
Gideon Giacomelli, Charité Berlin, Germany
Sjur Gjerald, Oslo University Hospital, Norway
Heather Grain, Llewelyn Grain Informatics, Australia
Evelyn Hovenga, EJSH Consulting, Australia
Christina Jaeger-Schmidt, Heidelberg University Hospital, Germany
Florian Kaercher, Charité Berlin, Germany
Heather Leslie, Atomica Informatics, Australia (openEHR Editor)
Cecilia Mascia, CRS4, Italy (openEHR Editor)
Shane McKee, Belfast Health & Social Care Trust, United Kingdom
Ian McNicoll, freshEHR Clinical Informatics, United Kingdom (openEHR Editor)
Andrej Orel, Marand d.o.o., Slovenia
Niklas Reimer, Institut für Medizinische Informatik / Universität zu Lübeck, Germany
Simon Schumacher, HiGHmed, Germany
Natalia Strauch, Medizinische Hochschule Hannover, Germany
Nyree Taylor, Ocean Informatics, Australia
Aurelie Tomczak, Uniklinikum Heidelberg, Germany (openEHR Editor)
Paolo Uva, CRS4, Italy
John Tore Valand, Helse Bergen, Norway
Gianluigi Zanetti, CRS4, Italy
Translators
  • German: Aurelie Tomczak, Natalia Strauch, Institute of Pathology, University Hospital Heidelberg, Medizinische Hochschule Hannover, au.tomczak@yahoo.com, Strauch.Natalia@mh-hannover.de
  • Norwegian Bokmål: Vebjørn Arntzen / Liv Laugen, ​Oslo University Hospital, Norway, varntzen@ous-hf.no, liv.laugen@ous-hf.no