Genomics Reporting Implementation Guide (STU1)

Genomics Reporting Implementation Guide, published by HL7 International Clinical Genomics Work Group. This is not an authorized publication; it is the continuous build for version 1.0.0). This version is based on the current content of https://github.com/HL7/genomics-reporting/ and changes regularly. See the Directory of published versions

Glossary

The following table represents most of the codeableConcepts presented in this guide and identifies corresponding profiles and valuesets where possible. View the individual profiles and sections under 'quick links' for more information on suggested usage.

Profile Display and Code Description Sample Values Value Set Value IDs
variant
(code)
Genetic variant assessment (69548-6) This profile is used to convery the presence or absence of a particular variant. Of note, 'No Call' is different from 'Absent', because 'No Call' did not result in the determination of the marker's presents or absents. This may be due to test failure or specimen specific context which renders the test ineffective. If not searching for specific variations and merely reporting what's found, the profile's value should be set to "Present". Details about the specific variant in consideration must be populated in the relevant components where available. Indeterminate, No call, Present, Absent LL1971-2 LA11884-6, LA18198-4, LA9633-4, LA9634-2
variant method (N/A) Indicates the method of variant analysis. This list is currently extensible, allowing for codification of other method types here at varying degrees of granularity. The work group is considering additional approaches to modeling testing methods and is requesting implementer feedback at this time. Sequencing, Oligo aCGH, SNP array, BAC aCGH, Curated, Digital array, FISH, Gene expression array, Karyotyping, MAPH, MALDI-TOF, Multiple complete digestion, MLPA, Optical mapping, PCR, qPCR (real-time PCR), ROMA, Merging, Denaturing high-pressure liquid chromatography (DHPLC), DNA hybridization, Computational analysis, Single-stranded conformational polymorphism (SSCP), Restriction fragment length polymorphism (RFLP) LL4048-6 LA26398-0, LA26399-8, LA26400-4, LA26401-2, LA26402-0, LA26403-8, LA26404-6, LA26405-3, LA26406-1, LA26407-9, LA26408-7, LA26414-5, LA26415-2, LA26417-8, LA26418-6, LA26419-4, LA26420-2, LA26808-8, LA26809-6, LA26810-4, LA26811-2, LA26812-0, LA26813-8
variant DNA change (c.HGVS) (48004-6) Human Genome Variation Society (HGVS) nomenclature for a single DNA marker. The 'c' here denotes a coding sequence, (strings in HGVS notation starting with "c.", e.g., c.78G>T) HGVS N/A
variant DNA change type (48019-4) Codified type for associated DNA change. The concurrent use of this code along with an HGVS component will display a standard and explicit type for convenience. To avoid duplication of efforts, we have bound this element to sequence ontology, specifically any terms under SO:0002072, "sequence_comparison". Duplication, Insertion, Insertion/Deletion, Inversion, Substitution, Deletion, Wild type, etc (all terms under SO:0002072) SO:0002072 (too many to list)
variant functional annotation (tbd) Annotated changes to sequence features caused by this variant. Values are from the sequence ontology under SO:0001537, "structural_variant". stop lost, stop gained, silent mutation, feature amplification, gene fusion, etc (all terms under SO:001537). SO:0001537 (too many to list)
variant Simple var ID (81252-9) This term is used to report the unique identifier of the simple variant found in this study. The identifier may come from various sources, including NCBI's ClinVar and Ensembl. For example, the variant NM_014049.4(ACAD9):c.1249C>T (p.Arg417Cys) has the ClinVar ID 30880 and would be reported in OBX-5 as 30880^NM_014049.4(ACAD9):c.1249C>T (p.Arg417Cys)^ClinVar. [http://www.ncbi.nlm.nih.gov/clinvar/variation/30880/] Typically only one code would be present, though multiple codings expressing the variant in different code systems are possible. See Appendix D for more information on code systems. (ClinVar IDs, eg) clinvar, eg (too many to list)
variant dbSNP ID (81255-2) The dbSNP ID is used routinely as the base identifier in pharmacogenomics as well as arrCGH studies. For example, for the simple variant NM_014049.4(ACAD9):c.1249C>T (p.Arg417Cys), the dbSNP ID is 368949613. [http://www.ncbi.nlm.nih.gov/clinvar/variation/30880/]. Note that the dbSNP ID alone does not fully describe the change, just its location and length. (dbSNP IDs) dbSNP (too many to list)
variant Genomic DNA change (g.HGVS) (81290-9) The name of a genomic/structural variant reported using HGVS nomenclature. (strings in HGVS notation starting with "g.", e.g., g.35476G>T) HGVS N/A
variant Genomic source class [Type] (48002-0) The genomic class of the specimen being analyzed: Germline for inherited genome, somatic for cancer genome, and fetal for prenatal genome. Fetal, Likely germline, Likely somatic, Likely fetal, Unknown genomic origin, De novo, Germline, Somatic LL378-1 LA10429-1, LA18194-3, LA18195-0, LA18196-8, LA18197-6, LA26807-0, LA6683-2, LA6684-0
variant Amino acid change (p.HGVS) (48005-3) Human Genome Variation Society (HGVS) nomenclature for an amino acid sequence. This value is derivable from the DNA Marker values if available. It is provided for convenience. The use of the nomenclature must be extended to describe non-variations (aka. wild types) see samples for wild type examples. (strings in HGVS notation starting with "p.", e.g., p.(Arg727Ser)) HGVS N/A
variant Amino acid change [Type] (48006-1) Codified type for associated Amino Acid Marker. Amino Acid Marker's use the HGVS notation which implies the Amino Acid Marker Type, but the concurrent use of this code will allow a standard and explicit type for technical and display convenience. Duplication, Insertion, Deletion, Frameshift, Initiating Methionine, Missense, Nonsense, Silent, Stop Codon Mutation, Wild type, Insertion and Deletion LL380-7 LA6686-5, LA6687-3, LA6692-3, LA6694-9, LA6695-6, LA6698-0, LA6699-8, LA6700-4, LA6701-2, LA9658-1, LA9659-9
variant Transcript ref sequence ID (51958-7) This field carries the ID for the transcribed reference sequence, which is the part of the genomic reference sequence that is converted to messenger RNA (i.e., after the introns are removed). For this ID use either the NCBI genomic nucleotide RefSeq IDs with their version number (see: NCBI.NLM.NIH.Gov/RefSeq). The transcript reference sequence ID may be reporting using various coding systems including NCBI's RefSeq ("NM_..."), Ensembl ("ENST..."), and LRG ("LRG..." plus "t1" to indicate transcript). See Appendix D for more information on code systems. (too many to list)
variant Genomic reference sequence ID (48013-7) This field carries the ID for the genomic reference sequence. The genomic reference sequence is a contiguous stretch of chromosome DNA that spans all of the exons of the gene and includes transcribed and non transcribed stretches. For this ID use either the NCBI genomic nucleotide RefSeq IDs with their version number (see: NCBI.NLM.NIH.Gov/RefSeq) or use the LRG identifiers, without transcript (t or p) extensions -- when they become available. The NCBI RefSeq genomic IDs are distinguished by a prefix of "NG" for genes from the nuclear chromosomes and prefix of "NC" for genes from mitochondria. The LRG Identifiers have a prefix of "LRG_". See Appendix D for more information on code systems. (too many to list)
variant Sample variant allelic frequency [NFr] (81258-6) The fraction of all reads in a study sample at a given genomic locus that identify the allele (variant) in question. quantity N/A N/A
variant Allelic read depth (82121-5) Specifies the number of reads that identified the allele in question whether it consists of one or a small sequence of contiguous nucleotides. Different methods and purposes require different numbers of reads to be acceptable. Often >400, sometimes as few as 2-4. counts N/A N/A
variant Allelic state (53034-5) The level of occurrence of a single DNA Marker within a set of chromosomes. Heterozygous indicates the DNA Marker is only present in one of the two genes contained in homologous chromosomes. Homozygous indicates the DNA Marker is present in both genes contained in homologous chromosomes. Hemizygous indicates the DNA Marker 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 Marker is present in some but not all of the copies of mitochondrial DNA. Homoplasmic indicates that the DNA Maker is present in all of the copies of mitochondrial DNA. Heteroplasmic, Homoplasmic, Homozygous, Heterozygous, Hemizygous LL381-5 LA6703-8, LA6704-6, LA6705-3, LA6706-1, LA6707-9
variant Gen struct var copy num (82155-3) The copy number of the large variant. In HGVS, this is the numeric value following the “X”. It is a unit-less value. Note that a copy number of 1 implies a deletion. The copy number can usually be inferred from the HGVS or ISCN fields. counts N/A N/A
variant Ref nucleotide (69547-8) Reference values ("normal") examined within the DNA Reference Sequence. This is used in a genotyping test to define the reference and variable nucleotide strings. That is if the sequence variation is an insertion, then Reference Nucleotide will be blank and Variable Nucleotide will contain the inserted nucleotides. In contrast, if the sequence variation is a deletion, then the Reference Nucleotide will contain the deleted nucliotieds, and the Variable Nucleotide will be blank. string N/A N/A
variant Alt allele (69551-0) The genomic alternate allele is the contiguous segment of DNA in the test sample that differs from the reference allele at the same location and thus defines a variant. string N/A N/A
variant Genomic coordinate system [Type] (92822-6) Base number of coordinate system either 0-based, with inclusive start and exclusive end (called interval), or 1-based, with inclusive start and end. However, two versions of 1-based are in common use. These systems are HGVS 1-based (called variant method) and VCF 1-based (called alignment method). In general, HGVS recommends right-justification and VCF recommends left-justification. However, these systems further address questions such as wheather or not to place an insertion before or after the nucleotide, and, if always placed before the nucleotide, how to handle insertion after the end of the sequence. Additionally, the systems deal with handling boundary effects of numbers between features. For more details see the HGVS and VCF guides. 0-based interval counting, 0-based character counting, 1-based character counting LL5323-2 LA30100-4, LA30101-2, LA30102-0
variant exact start-end (81254-5) Also known as Gen allele loc ID, the genomic allele location is the first genomic position in the reference that contains a change. Use this component when the exact endpoints for the change are known. For a variant where the change is only one base long, the 'high' value of the range need not be sent. For example, for the simple variant NM_014049.4(ACAD9):c.1249C>T (p.Arg417Cys), the 'low' genomic allele location is 128906220 (on Chr3 in Assembly GRCh38, 1-based character counting). The 'high' value need not be sent. (low count, optional higher count) N/A N/A
variant Variant length (81300-6) Previously called Struct var len, the length of the variant, which information may be ascertained in some but not all types of variants. (count) N/A N/A
variant Variant outer start-end (81301-4) The genomic coordinates of the widest genomic range in which the variant might reside. Used when the exact boundaries of the variant are not clear. (low count, higher count) N/A N/A
variant Variant inner start-end (81302-2) The genomic coordinates of the narrowest genomic range in which the variant might reside. Used when the exact boundaries of the variant are not clear. (low count, higher count) N/A N/A
variant Chromosome copy number change [Type] (62378-5) The type of the chromosome copy number change. Copy number gain, Copy number loss LL1041-4 LA14033-7, LA14034-5
variant Struct var rep arrCGH Rto (81299-0) For a Comparative genomic hybridization array test, the resulting ratio of the fluorescence intensities, which is proportional to the ratio of the copy numbers of DNA sequences in the test and reference genomes. (quantity) N/A N/A
variant Complex variant type (81263-6) The type of complex variant, for example, compound heterozygous or haplotype. When sending a grouping of non-contiguous variants that are meant to be interpreted together but do not signify a named haplotype, one can send the type of complex variant here (determined by where the individual changes are in relation to each other), and use Observation.hasMember to reference the individual variants, which would then be described as normal. Compound heterozygous, Haplotype, Double heterozygous, Hemizygous LL3999-1 LA26217-2, LA26218-0, LA26220-6, LA6707-9
variant Struct var ISCN (81291-7) Fully describes a variant with a single code in the International System for Human Cytogenetic Nomenclature. Typically a large aberrant variant such as a mosaic, abnormal chromosome numbers, etc. See Appendix D for more information on code systems. N/A ISCN N/A
implication Level of evidence (93044-6) Indicates the quality and type of evidence supporting this assertion. E.g. terms from ACMG guidelines for the interpretation of sequence variants or CPIC Clinical Annotation levels of Evidence. Uncertain significance, Very strong evidence pathogenic, Strong evidence pathogenic, Moderate evidence pathogenic, Supporting evidence pathogenic, Supporting evidence benign, Strong evidence benign, Stand-alone evidence pathogenic, Stand-alone evidence benign LL5356-2 LA26333-7, LA30200-2, LA30201-0, LA30202-8, LA30203-6, LA30204-4, LA30205-1, LA30206-9, LA30207-7
finding Gene studied ID (48018-6) HUGO Gene Nomenclature Committee (HGNC) identifier for a gene. List the gene(s) examined in full or in part by the study. If the study addresses multiple genes, these can be recorded in multiplegene studied components. The required codingwill use the HGNC gene symbol as the display text and HGNC gene ID as the code, eg code=HGNC:1100, display="BRCA1". N/A HGNC gene IDs N/A
finding Cyto loc ID (48001-2) Cytogenetic chromosome location is where the genomic finding took place, providing information such as the chromosome id and other positional information. (e.g. "chr2", "chrX", "2p16.3", etc) (N/A)
finding Human reference sequence assembly version (62374-4) The version of the human reference sequence assembly (extensible). GRCh37, NCBI Build 36.1, NCBI Build 35, NCBI Build 34 LL1040-6 LA14029-5, LA14030-3, LA14031-1, LA14032-9
inh-dis-path Genetic variation clinical significance [Imp] (53037-8) Single DNA marker or individual allele interpretation in the context of the assessed genetic disease. Likely pathogenic, Uncertain significance, Likely benign, Pathogenic, Benign LL4034-6 LA26332-9, LA26333-7, LA26334-5, LA6668-3, LA6675-8
inh-dis-path Prob assoc phenotype (81259-4) The possible phenotype associated with the genetic variant found in this study. If sending multiple phenotypes, break up the assertions based on the independently assessed conditions, whether they be a single term or a collection of co-occurring terms. N/A (HPO, eg) N/A
interpretation Discrete variation analysis overall interpretation (51968-6) Interpretation of all identified DNA Markers and/or Individual Alleles along with any known clinical information for the benefit of aiding clinicians in understanding the results overall. This is used for Symptomatic or Asymptomatic testing other than Carrier testing. Positive, Negative, Inconclusive, Failure LL541-4 LA6576-8, LA6577-6, LA9663-1, LA9664-9
genotype Genotype name (84413-4) The specific genotype observed
haplotype Haplotype name (84414-2) The specific haplotype observed
haplotype Haplotype method (N/A) Indicates the method used to determine the haplotype Directly measured, Family DNA, Family history, Inferred from population data LL4050-2 LA26426-9, LA26427-7, LA26428-5, LA26429-3
seq-phase-reltn Allelic phase (82120-7) Indicates whether entities are in Cis (same strand) or Trans (opposite strand) relationship to each other . NOTE, implementors must be careful to not describe more observations as in-trans than are appropriate.In a typical diploid, this would be at most two expressed as in-trans with each other.This 0..* relationship allows for any number of items to be expressed as in-cis. Maternal, Paternal, 1st set of variants in cis relation to each other, 2nd set of variants in cis relation to each other, 3rd set of variants in cis relation to each other, 4th set of variants in cis relation to each other, 5th set of variants in cis relation to each other, Unknown, Other LL4025-4 LA26320-4, LA26321-2, LA26814-6, LA26815-3, LA26816-1, LA26817-9, LA26818-7, LA4489-6, LA46-8
pgx Medication assessed (51963-7) The medication whose impact is being described (RxNorm, eg)
metabolism Genetic variation's effect on drug metabolism (53040-2) Predicted phenotype for drug efficacy. A single marker interpretation value known to allow (responsive) or prevent (resistant) the drug to perform. Ultrarapid metabolizer, Intermediate metabolizer, Rapid metabolizer, Normal metabolizer, Poor metabolizer LL3856-3 LA10315-2, LA10317-8, LA25390-8, LA25391-6, LA9657-3
efficacy Genetic variation's effect on drug efficacy (51961-1) Predicted phenotype for ability of drug to bind to intended site in order to deliver intended affect. A single marker interpretation value known to allow (responsive) or prevent (resistant) the drug to perform. Drug efficacy marker interpretation, based on LOINC LL539-8. Look to http://build.fhir.org/ig/HL7/genomics-reporting/task-med-chg.html for guidance. If the variant is predicted to not have an effect then Responsive is the proper choice. Non-responsive implies complete resistance, whereas Resistant indicates residual drug efficacy. Presumed Benign, Benign, Resistant, Responsive, Unknown Significance, Presumed resistant, Presumed responsive, Presumed non-responsive LL539-8 LA6674-1, LA6675-8, LA6676-6, LA6677-4, LA6682-4, LA9660-7, LA9661-5, LA9662-3
transporter Genomic variation's effect on transporter function (tbd) Predicted phenotype for drug efficacy through transport mechanism. A single marker interpretation value known to increase or decrease the drug's performance. Source of list: https://www.nature.com/articles/gim201687/tables/2 Increased function, Normal function, Decreased function, Poor function
high-risk Genetic variation's effect on high-risk allele (83009-1) High risk, Low risk LL2353-2 LA19541-4, LA19542-2
region-studied DNA region of interest (53041-0) The Region Studied profile is used to assert actual regions studied for the performed test(s). Intended coverage areas may differ from actual coverage areas (e.g. due to technical limitations during test performance). This Obvservation does not carry a value. N/A - no value N/A N/A - no value
region-studied Gene Mutations (36908-2) Also known as "Gene Mut Tested Bld/T", specific Gene mutations that were tested for N/A HGVS N/A
region-studied Region coverage (tbd) When sequencing, what % of the region was covered N/A % N/A
region-studied Region description (81293-3) Also known as "DNA range(s) examined Nar", description of the region examined N/A (string) N/A
region-studied DNA region of interest NumRange (51959-5) This term is used to report the region(s) of interest for sequencing studies as one or more numeric ranges that identify the parts of the reference sequence that are sequenced. These can be recorded as one or more HL7 numeric ranges using repeat delimiters to seperate multiple such ranges (use along with 92822-6 and 48013-7). N/A (ranges) N/A
somatic-diagnostic (tbd profile code) Finding of whether a particular somatic genotype/haplotype/variation or combination-thereof supports or opposes the diagnosis of a particular cancer . Indicates the diagnostic predictive nature of the associated genomic findings for the specified cancer - i.e. patient definitely has/may have/definitely doesn't have. E.g. Pathognomonic, Supportive, Argues Against, Rules Out
somatic-prognostic (tbd profile code Finding of whether a particular somatic genotype/haplotype/variation or combination-thereof predicts a particular outcome for the specified cancer - either on its own or in conjunction with one or more interventions . The predicted outcome for the cancer either on its own or in conjunction with the specified intervention(s) E.g. Better outcome, poorer outcome
somatic-prognostic medication (tbd) The medication or medication class whose implication on the cancer outcome is being predicted. If multiple medications and/or therapies are present, the implication asserted represents the implication of the combination of interventions.
somatic-prognostic therapy (tbd) The non-medication therapy whose implication on the cancer outcome is being predicted.E.g. altered diet, radiation therapy, surgery, etc. If multiple medications and/or therapies are present, the implication asserted represents the implication of the combination of interventions.
somatic-predictive (tbd profile code) Finding of whether a particular somatic genotype/haplotype/variation or combination-thereof predicts the impact of a specified medication or combination of medications E.g. Resistant, Responsive, Not-Responsive, Sensitive, Reduced-Sensitivity, Adverse Response