Cascade Protocol Genomics Ontology
type: Ontology
imports: v1#
description: Layer 2 vocabulary for sequence variants, variant interpretations, haplotypes/diplotypes, copy number variants, sequencing-run metadata, raw-file pointers, pedigrees, and genetic test reports/orders. Bridges Layer 1 standards (HGVS, ClinVar, VRS, HGNC, Sequence Ontology, HPO, MONDO/OMIM/ORDO, ACMG/AMP via LOINC answer codes, ClinGen review-status taxonomy) to Layer 3 patient-facing genetic counseling summaries in checkup:.
creator: Cascade Agentic Labs
created: 2026-05-05
modified: 2026-06-16
version info: 1.0-draft
comment: DRAFT — pre-stable v1 ontology. Property names, ranges, and structure may change before v1.0 stable release. Three-layer ontology for genomics: Layer 1 (Established): HGVS nomenclature, VRS, ClinVar, HGNC, Sequence Ontology, HPO, MONDO/OMIM/ORDO, ACMG/AMP (encoded via LOINC), ClinGen review-status taxonomy, GA4GH htsget streaming. Layer 2 (genomics:): Variant, VariantInterpretation, SubmitterAssertion, Haplotype, Diplotype, CopyNumberVariant, SequencingRun, RawFile, GeneticTest, GeneticTestOrder, Pedigree, PedigreeMember — RDF resources binding Layer 1 codes to a patient and family with provenance and quality tier. Layer 3 (checkup:): GeneticCounselingSummary, VariantNarrative — patient-facing aggregations and regeneratable narrative (authored separately in the checkup vocabulary).

Sequence Variant
type: Class
comment: A specific sequence variant observed in a patient sample. Carries the four parallel descriptions of variant identity (HGVS for human readability, ClinVar/VRS for stable computable identity, Sequence Ontology for consequence type, gene for biological context). Distinct from VariantInterpretation, which assigns clinical significance.
subclass of: Observation
subclass of: Entity
subclass of: Restriction
  on property: Gene Symbol (HGNC Approved)
  cardinality: 1

Variant Interpretation
type: Class
comment: A clinical-significance assertion linking a Variant to a single condition (per D-Q5 — multi-condition cases produce multiple Interpretation instances), with ACMG/AMP classification, supporting criteria, and an interpreting laboratory or expert panel. Reclassifications produce new Interpretation instances linked to the prior via prov:wasRevisionOf — interpretations are versioned, not edited. SHACL enforces genomics:condition and genomics:variantInterpreted both at cardinality 1..1 (see genomics.shapes.ttl, TASK-0.2).
subclass of: Observation
subclass of: Entity

Genetic Test Report
type: Class
comment: Result envelope from a clinical genetic test (panel, exome, single-gene). Aggregates Variant observations, gene panel scope, methodology, and ordering provider. Maps to FHIR DiagnosticReport. For test orders that have not yet resulted, see genomics:GeneticTestOrder.
subclass of: DiagnosticReport
subclass of: Entity

Genetic Test Order
type: Class
comment: An order/request for a genetic test, distinct from the resulting GeneticTest. Maps to FHIR ServiceRequest. Counseling workflows track 'ordered but not yet resulted' state via this class. Once the order is fulfilled, link the resulting GeneticTest via genomics:resultedIn.
subclass of: ServiceRequest
subclass of: Entity

Gene
type: Class
comment: A gene reference, identified by HGNC approved symbol and ID. Used as the target of variant observations and gene-disease associations.

Haplotype
type: Class
comment: A multi-variant unit travelling together on one chromosome — the unit of clinical interpretation in pharmacogenomics (PharmVar star alleles like CYP2C19*2, CYP2D6*4) and HLA typing (HLA-DQB1*02:01). Cannot be expressed as a single Variant. Anchored on fhir:Observation per FHIR Genomics IG haplotype profile.
subclass of: Observation
subclass of: Entity

Diplotype
type: Class
comment: A pair of haplotypes (e.g., '*1/*2'), required for any pharmacogenomics or HLA typing use case. Anchored on fhir:Observation per FHIR Genomics IG genotype profile.
subclass of: Observation
subclass of: Entity

Copy Number Variant
type: Class
comment: A structural variant defined by deletion or duplication of a genomic interval, expressed as integer copy number plus interval coordinates rather than HGVS. Required for structural-variant cases (e.g., 13q14 deletion in retinoblastoma). subClassOf genomics:Variant — inherits stable-ID and zygosity properties where applicable.
subclass of: Sequence Variant

Sequencing Run
type: Class
comment: Metadata for a single sequencing run that produced one or more variants. Captures coverage depth, technology, variant-caller version, laboratory certification, and key dates (sample collection, sequencing, file generation). Used to populate the data-quality tier on derived Variants and to trace provenance back to lab process.
subclass of: Activity

Raw Genomic File
type: Class
comment: Pointer-and-hash record for a raw genomic file (BAM, CRAM, FASTQ, gVCF, VCF, BCF). Cascade does NOT ingest the bytes — only the manifest. The bytes live wherever the user keeps them (lab cloud, local disk, NAS, htsget-served). genomics:fileLocation may be opaque (s3://, https://, file://, or a vendor-specific URI) and is not validated by Cascade.
subclass of: Entity

HGVS Coding-DNA Description
type: DatatypeProperty
comment: Variant described against a coding-sequence (transcript) reference, e.g. 'NM_000059.4:c.5946delT'. Includes transcript accession with version. This is the form most often cited in clinical reports.
domain: Sequence Variant
range: string
LOINC Code Annotation: http://loinc.org/rdf#48004-6

HGVS Protein Description
type: DatatypeProperty
comment: Variant described at the protein level, e.g. 'NP_000050.3:p.Ser1982Argfs*22'. Use parentheses (p.(Ser1982Argfs*22)) when the protein consequence is predicted from the DNA change rather than directly observed.
domain: Sequence Variant
range: string
LOINC Code Annotation: http://loinc.org/rdf#48005-3

HGVS Genomic Description
type: DatatypeProperty
comment: Variant described against a genomic reference, e.g. 'NC_000013.11:g.32340301del'. Required for cross-transcript joins and for variants outside coding regions.
domain: Sequence Variant
range: string
LOINC Code Annotation: http://loinc.org/rdf#81290-9

Reference Allele
type: DatatypeProperty
comment: The reference base sequence at the variant position, as defined by the reference genome assembly. ATCG[N], typically 1–N bases. Per VCF REF / FHIR Genomics IG LOINC 69547-8.
domain: Sequence Variant
range: string
LOINC Code Annotation: http://loinc.org/rdf#69547-8

Alternate Allele
type: DatatypeProperty
comment: The variant allele sequence at the variant position. ATCG[N] for substitutions/insertions; '-' or empty for deletions; structured forms like ' '/'<DUP>' for symbolic alleles. Per VCF ALT / FHIR Genomics IG LOINC 69551-0.
domain: Sequence Variant
range: string
LOINC Code Annotation: http://loinc.org/rdf#69551-0

Genomic Start-End Coordinates
type: DatatypeProperty
comment: The 1-based inclusive start-end coordinates of the variant on the reference assembly, formatted as 'chrN:start-end' (e.g., 'chr17:43124027-43124028'). Pair with genomics:referenceGenome for full anchoring. Per FHIR Genomics IG LOINC 81254-5.
domain: Sequence Variant
range: string
LOINC Code Annotation: http://loinc.org/rdf#81254-5

Protein Consequence Directly Observed
type: DatatypeProperty
comment: True when the p.HGVS description was directly observed at the protein level (e.g. mass spec, functional assay). False or absent means the protein consequence was predicted from the DNA change. Conventionally encoded in HGVS by parentheses around the p. description.
domain: Sequence Variant
range: boolean

Reference Transcript
type: DatatypeProperty
comment: RefSeq transcript accession with version, e.g. 'NM_000059.4'. Stored separately from the HGVS string so that downstream tools can reason about transcript version drift, the most common source of variant ambiguity in clinical handoffs.
domain: Sequence Variant
range: string

Reference Genome Assembly
type: DatatypeProperty
comment: Reference genome build, e.g. 'GRCh38' or 'GRCh37'. Required when interpreting g.HGVS coordinates.
domain: Sequence Variant
range: string

ClinVar Variation ID
type: DatatypeProperty
comment: ClinVar VCV accession identifying the variant (not the variant-condition pair). Example: 'VCV000051062' for BRCA2 c.5946delT.
domain: Sequence Variant
range: string
LOINC Code Annotation: http://loinc.org/rdf#81252-9

ClinVar RCV ID
type: DatatypeProperty
comment: ClinVar RCV accession identifying a variant-condition assertion. Multiple RCVs typically attach to one VCV. Lives on VariantInterpretation, not Variant.
domain: Variant Interpretation
range: string

dbSNP rsID
type: DatatypeProperty
comment: NCBI dbSNP reference SNP identifier, e.g. 'rs80359550'. Primary join key for consumer-array (23andMe / AncestryDNA / etc.) imports.
domain: Sequence Variant
range: string

ClinGen Allele Registry CAid
type: DatatypeProperty
comment: ClinGen Allele Registry canonical allele identifier. Stable across HGVS reformulations and assembly changes — the recommended primary join key when available.
domain: Sequence Variant
range: string

GA4GH VRS Identifier
type: DatatypeProperty
comment: Deterministic computable hash identifier per GA4GH Variation Representation Spec. Computed from the normalized sequence-location-state object; identical variants always hash to the same VRS ID regardless of how they were originally described.
domain: Sequence Variant
range: string

VRS Allele Object (JSON-LD)
type: DatatypeProperty
comment: Full VRS Allele JSON-LD payload as serialized string. Carries sequence reference, location interval, and state. Permits round-trip to other VRS-aware systems without re-parsing the HGVS.
domain: Sequence Variant
range: string

Gene Symbol (HGNC Approved)
type: DatatypeProperty
comment: HGNC approved gene symbol, e.g. 'BRCA2'. Always use the approved symbol, never an alias.
domain: Sequence Variant
range: string
LOINC Code Annotation: http://loinc.org/rdf#48018-6

HGNC ID
type: DatatypeProperty
comment: HGNC numeric identifier with prefix, e.g. 'HGNC:1101' for BRCA2. Stable across symbol changes.
domain: Sequence Variant
range: string

Sequence Ontology Consequence
type: ObjectProperty
comment: Sequence Ontology term URI describing the molecular consequence of the variant, e.g. so:0001589 (frameshift_variant), so:0001583 (missense_variant), so:0001587 (stop_gained).
domain: Sequence Variant
range: Class

Consequence Label
type: DatatypeProperty
comment: Human-readable consequence label paired with the SO URI for legibility, e.g. 'frameshift_variant'.
domain: Sequence Variant
range: string

Zygosity
type: ObjectProperty
comment: Zygosity of the observed variant. Named-individual values: genomics:Heterozygous, Homozygous, Hemizygous, CompoundHeterozygous, MosaicLow, MosaicHigh. For mosaic variants, also populate genomics:mosaicismFraction with the actual VAF.
domain: Sequence Variant
range: Zygosity Value
LOINC Code Annotation: http://loinc.org/rdf#53034-5

Mosaicism Fraction (VAF)
type: DatatypeProperty
comment: Variant allele fraction (0.0–1.0) for mosaic variants. Distinct from zygosity, which is categorical. The continuous VAF is the load-bearing number for clinical decisions in somatic mosaicism scenarios. NOTE (v1-draft.0.2): for the broader 'fraction of reads supporting alt allele' use genomics:variantAlleleFrequency; mosaicismFraction is reserved for the clinical conclusion that the variant is present in only a subset of cells.
domain: Sequence Variant
range: decimal

Variant Allele Frequency
type: DatatypeProperty
comment: Fraction of sequencing reads at the variant position that support the alternate allele. Range 0.0–1.0. Per FHIR Genomics IG LOINC 81258-6. Distinct from genomics:mosaicismFraction — VAF is a sequencing-evidence fraction; mosaicism is the clinical conclusion that the variant is present in only a subset of cells (which often, but not always, manifests as low VAF).
domain: Sequence Variant
range: decimal
LOINC Code Annotation: http://loinc.org/rdf#81258-6

Somatic Status
type: ObjectProperty
comment: Whether the variant is germline (inherited / present in all cells) or somatic (acquired / tissue-specific). Critical for cancer interpretation and inheritance reasoning. Per FHIR Genomics IG LOINC 48002-0.
domain: Sequence Variant
range: Somatic Status
LOINC Code Annotation: http://loinc.org/rdf#48002-0

Allelic Phase
type: ObjectProperty
comment: For compound heterozygous calls in the same gene: whether the two variants are in cis (same chromosome) or trans (opposite chromosomes). Values: genomics:Cis, Trans, PhaseUnknown. Critical for autosomal recessive inheritance interpretation.
domain: Sequence Variant
range: Allelic Phase Value

Phased With Variant
type: ObjectProperty
comment: Links to the partner Variant when phase has been determined for a compound-heterozygous pair. Symmetric (each variant phasedWith the other).
domain: Sequence Variant
range: Sequence Variant

Haplotype Component Variant
type: ObjectProperty
comment: Links a Haplotype to one of its component Variants. A haplotype is composed of multiple variants that travel together on one chromosome.
domain: Haplotype
range: Sequence Variant

Star Allele Symbol
type: DatatypeProperty
comment: PharmVar/HLA-style nomenclature, e.g. 'CYP2C19*2', 'HLA-DQB1*02:01'. The clinically actionable identifier in pharmacogenomics and HLA typing.
domain: Haplotype
range: string

Diplotype Notation
type: DatatypeProperty
comment: Compact paired-haplotype notation, e.g. '*1/*2'. Computed from hapA + hapB; carried as a string for human readability and direct match against PGx guideline tables.
domain: Diplotype
range: string

Haplotype A
type: ObjectProperty
comment: First haplotype of a diplotype pair. Order (A vs B) is arbitrary but must be stable within a record.
domain: Diplotype
range: Haplotype

Haplotype B
type: ObjectProperty
comment: Second haplotype of a diplotype pair.
domain: Diplotype
range: Haplotype

Copy Number
type: DatatypeProperty
comment: Integer copy number observed for the genomic interval, e.g. 1 (heterozygous deletion), 0 (homozygous deletion), 3 (single duplication), 4+ (amplification). Distinct from zygosity.
domain: Copy Number Variant
range: integer

CNV Interval Start
type: DatatypeProperty
comment: Start coordinate (1-based, inclusive) of the CNV interval on the reference indicated by cnvIntervalRef.
domain: Copy Number Variant
range: integer

CNV Interval End
type: DatatypeProperty
comment: End coordinate (1-based, inclusive) of the CNV interval.
domain: Copy Number Variant
range: integer

CNV Interval Reference
type: DatatypeProperty
comment: Genomic reference for the interval coordinates, e.g. 'NC_000013.11' (chromosome 13 in GRCh38) or a chromosome name. Required for downstream analyses to locate the interval.
domain: Copy Number Variant
range: string

Variant Interpreted
type: ObjectProperty
comment: The Variant being assessed by this VariantInterpretation. SHACL enforces cardinality 1..1 (per D-Q5).
domain: Variant Interpretation
range: Sequence Variant

ACMG/AMP Classification
type: ObjectProperty
comment: Five-tier ACMG/AMP classification. Named-individual values map 1:1 to LOINC answer codes: Pathogenic (LA6668-3), LikelyPathogenic (LA26332-9), VUS (LA26333-7), LikelyBenign (LA26334-5), Benign (LA6675-8).
domain: Variant Interpretation
range: ACMG Classification
LOINC Code Annotation: http://loinc.org/rdf#53037-8

ACMG Evidence Criteria
type: DatatypeProperty
comment: Space-separated ACMG/AMP evidence criteria codes applied in this classification, e.g. 'PVS1 PM2 PP5'. Order is not significant.
domain: Variant Interpretation
range: string

Associated Condition
type: ObjectProperty
comment: Disease or condition associated with this interpretation. Range is a MONDO/OMIM/ORDO term URI. Per D-Q5, each VariantInterpretation has cardinality 1..1 on this property — multi-condition cases produce multiple interpretation instances.
domain: Variant Interpretation
range: Class

MONDO Disease ID
type: DatatypeProperty
comment: MONDO disease ontology ID, e.g. 'MONDO:0007254' for Hereditary breast carcinoma.
domain: Variant Interpretation
range: string

OMIM Phenotype/Gene ID
type: DatatypeProperty
comment: OMIM identifier (six-digit) for a Mendelian phenotype or gene, e.g. '604370' for Breast-ovarian cancer, familial, susceptibility to, 2.
domain: Variant Interpretation
range: string

Orphanet Code
type: DatatypeProperty
comment: Orphanet rare disease code, e.g. 'ORPHA:145' for Hereditary breast and ovarian cancer syndrome.
domain: Variant Interpretation
range: string

Mode of Inheritance
type: ObjectProperty
comment: GenCC-aligned mode of inheritance for the gene-disease relationship. Named-individual values: AutosomalDominant, AutosomalRecessive, XLinkedDominant, XLinkedRecessive, Mitochondrial, YLinked, MultifactorialPolygenic, UnknownInheritance.
domain: Variant Interpretation
range: Mode of Inheritance

Allelic Requirement
type: ObjectProperty
comment: GenCC allelic requirement: monoallelic, biallelic, etc. Captures whether one or two copies of a pathogenic variant are required for the disease phenotype.
domain: Variant Interpretation
range: Allelic Requirement

Interpreting Laboratory or Expert Panel
type: DatatypeProperty
comment: Name of the lab, ClinGen Variant Curation Expert Panel (VCEP), or curator who issued this interpretation. Free-text for now; will be replaced with a fhir:Organization reference in v1.0.
domain: Variant Interpretation
range: string

Interpretation Date
type: DatatypeProperty
comment: Date this interpretation was issued. Reclassifications create new Interpretation instances; the date here is the date of THIS classification, not the original.
domain: Variant Interpretation
range: date

Submitter Assertion
type: Class
comment: A single submitter's assertion about a variant-condition pair, e.g. one ClinVar SCV record. Aggregated assertions roll up into a VariantInterpretation via genomics:aggregatedFrom. Individual submissions may disagree with the aggregate (most agree, but ENIGMA, Mayo, Ambry, etc. can each carry distinct opinions).
subclass of: Entity

Aggregated From
type: ObjectProperty
comment: Links a VariantInterpretation to the SubmitterAssertions it aggregates. The aggregate classification is computed from these per-submitter records; preserving the constituents lets downstream tools recompute or audit the rollup.
domain: Variant Interpretation
range: Submitter Assertion

Asserted ACMG Classification
type: ObjectProperty
comment: The ACMG class assigned by this individual submitter. May differ from the aggregate classification on the parent VariantInterpretation.
domain: Submitter Assertion
range: ACMG Classification

Submitter Name
type: DatatypeProperty
comment: Name of the submitting laboratory, consortium, or expert panel, e.g. 'ENIGMA', 'Ambry Genetics', 'Mayo Clinic'.
domain: Submitter Assertion
range: string

Submitter Organization ID
type: DatatypeProperty
comment: ClinVar OrgID (or equivalent submitter registry identifier) for the submitting organization.
domain: Submitter Assertion
range: string

Submitter Category
type: ObjectProperty
comment: Class of submitter: laboratory, consortium, expert-panel, research-group, single-clinician, etc. Drives review-status weighting.
domain: Submitter Assertion
range: Submitter Category

SCV Accession
type: DatatypeProperty
comment: ClinVar SCV (Submission) accession identifying this individual submission, e.g. 'SCV000123456'.
domain: Submitter Assertion
range: string

Contributes to Aggregate
type: DatatypeProperty
comment: True when this submission is included in the aggregate classification. Some submissions are excluded (withdrawn, superseded, flagged) but retained for audit.
domain: Submitter Assertion
range: boolean

Assertion Evidence Level
type: ObjectProperty
comment: Strength-of-evidence label per the submitter's review process. Range is a vocabulary-extensible class — no fixed enum to allow lab-specific gradings.
domain: Submitter Assertion

Review Status
type: ObjectProperty
comment: ClinGen / ClinVar review-status classification of this VariantInterpretation, mapping to the 0–4 star confidence rating. Drives advisory engine trust decisions.
domain: Variant Interpretation
range: Review Status

Star Rating
type: DatatypeProperty
comment: Integer 0–4 star rating associated with a ReviewStatus, matching ClinVar UI.
domain: Review Status
range: integer

Interpretation Status (Causality)
type: ObjectProperty
comment: Whether this variant explains THIS patient's phenotype. Distinct from ACMG classification: ACMG classifies the variant; interpretationStatus classifies the variant's role in the patient's clinical picture. Aligned with GA4GH Phenopackets v2 InterpretationStatus enum.
domain: Variant Interpretation
range: Causality Status

Genetic Test Type
type: ObjectProperty
comment: Test methodology category. Named-individual values: SingleGeneTest, GenePanelTest, ExomeSequencing, GenomeSequencing, ChromosomalMicroarray, KaryotypeAnalysis, MLPA, RepeatExpansionTest, MethylationStudy, RNASequencing.
domain: Genetic Test Report
range: Genetic Test Type

Gene Panel Members
type: DatatypeProperty
comment: Space-separated HGNC symbols for the genes included in this test's analytical scope. Used to distinguish 'no variant found in BRCA1/2' from 'no variant found across a 47-gene cancer panel'.
domain: Genetic Test Report
range: string

Variants Observed
type: ObjectProperty
comment: Variants reported by this test. Empty list with non-empty genePanel = clinically meaningful negative result.
domain: Genetic Test Report
range: Sequence Variant

Reported Record
type: ObjectProperty
comment: A genomics record (Variant, Haplotype, Diplotype, VariantInterpretation, or other genomics:* class) referenced by this GeneticTest. Use this predicate when the test result is a Diplotype, Haplotype, or PGx implication that has no Variant-typed range. For point-Variant references, prefer the type-specific genomics:variantsObserved (rdfs:range genomics:Variant).
domain: Genetic Test Report

Ordering Provider
type: DatatypeProperty
comment: Name of clinician who ordered the test. Will become a fhir:Practitioner reference in v1.0.
domain: Genetic Test Report
range: string

Performing Laboratory
type: DatatypeProperty
comment: Name of the laboratory that performed the analysis. Free-text for now; fhir:Organization reference in v1.0.
domain: Genetic Test Report
range: string

Ordered At
type: DatatypeProperty
comment: Timestamp when the test was ordered.
domain: Genetic Test Order
range: dateTime

Order Status
type: ObjectProperty
comment: Status of the test order: Pending, InProgress, Resulted, Cancelled.
domain: Genetic Test Order
range: Order Status

Resulted In
type: ObjectProperty
comment: Links a fulfilled GeneticTestOrder to the resulting GeneticTest.
domain: Genetic Test Order
range: Genetic Test Report

Coverage Depth
type: DatatypeProperty
comment: Mean coverage depth across the targeted region, e.g. 30.0 for typical clinical WGS. ClinicalGrade tier requires >=30x for WGS or validated panel-specific equivalents.
domain: Sequencing Run
range: decimal

Sequencing Technology
type: ObjectProperty
comment: Sequencing platform/technology category. Named-individual values: ShortReadIllumina, LongReadONT, LongReadPacBio, Mixed, GenotypingArray.
domain: Sequencing Run
range: Sequencing Technology

Variant Caller Version
type: DatatypeProperty
comment: Variant caller name and version, e.g. 'GATK 4.5.0', 'DeepVariant 1.6'. Important for reproducibility and for distinguishing caller-driven differences from biological ones.
domain: Sequencing Run
range: string

Laboratory Certification
type: ObjectProperty
comment: Regulatory certification of the performing laboratory. Named-individual values: CLIA, CAP, ISO15189, Uncertified.
domain: Sequencing Run
range: Laboratory Certification

Sample Collection Date
type: DatatypeProperty
comment: Date the biological sample was collected from the patient.
domain: Sequencing Run
range: date

Sequencing Date
type: DatatypeProperty
comment: Date sequencing was performed on the sample.
domain: Sequencing Run
range: date

File Generation Date
type: DatatypeProperty
comment: Date the raw genomic file (BAM/CRAM/VCF/etc.) was generated. May post-date sequencingDate by re-alignments or re-calls.
domain: Sequencing Run
range: date

File Format
type: ObjectProperty
comment: Raw genomic file format. Named-individual values: BAM, CRAM, FASTQ, gVCF, VCF, BCF, Other. Hot tier (in-pod, encrypted): VCF, gVCF, BCF. Cold tier (out-of-pod, referenced): BAM, CRAM, FASTQ.
domain: Raw Genomic File
range: File Format

File Size (Bytes)
type: DatatypeProperty
comment: Size of the raw file in bytes. xsd:long because BAM/CRAM/FASTQ files routinely exceed 2^31 bytes (50–100 GB+).
domain: Raw Genomic File
range: long

File SHA-256 Hash
type: DatatypeProperty
comment: Lowercase hex-encoded SHA-256 digest of the file contents. Integrity check enabling the pod to verify the bytes-on-disk match the manifest.
domain: Raw Genomic File
range: string

File Location URI
type: DatatypeProperty
comment: Opaque pointer to where the bytes live (s3://, https://, file://, vendor-specific). Cascade does NOT validate or fetch this URI; the bytes live wherever the user keeps them. See Critical conventions #9.
domain: Raw Genomic File
range: anyURI

Reference Genome
type: DatatypeProperty
comment: Reference assembly the file is aligned against, e.g. 'GRCh38', 'GRCh37', 'T2T-CHM13'. Required for any downstream coordinate-based analysis.
domain: Raw Genomic File
range: string

htsget Endpoint
type: DatatypeProperty
comment: Optional GA4GH htsget endpoint URI for streaming BAM/CRAM regions on demand without ingesting the full file. Letters labs and cloud-genomics services typically expose htsget; consumer providers usually do not.
domain: Raw Genomic File
range: anyURI

Genomic Data Provenance
type: ObjectProperty
comment: Origin lane of the genomic data, driving importer routing and quality-tier inference. Named-individual values: ConsumerArray, ClinicalSequencing, ResearchSequencing, Imported, AIExtracted. Distinct from the broader cascade:dataProvenance (consumer-vs-clinical classification) — this is genomics-specific because consumer-array imports (Phase 2C) need a distinct lane that auto-tags ConsumerGrade quality.
range: Genomic Data Provenance

Data Quality Tier
type: ObjectProperty
comment: Quality tier of the genomic data underlying this Variant, driving downstream advisory and narrative subsystems. Named-individual values: ClinicalGrade, ResearchGrade, ConsumerGrade, UnknownQuality. Aligns with cascadeprotocol.org sequencing-provider directory's three quality criteria (>=30x coverage + raw files + CLIA-certified).
domain: Sequence Variant
range: Data Quality Tier

Requires Confirmation
type: DatatypeProperty
comment: True when this VariantInterpretation requires confirmatory clinical-grade re-testing before it can drive care decisions. SHACL (TASK-0.2): any Pathogenic / LikelyPathogenic interpretation MUST either reference a ClinicalGrade Variant OR carry requiresConfirmation true. The advisory engine MUST NOT auto-apply care recommendations to confirmation-required interpretations regardless of issuer trust.
domain: Variant Interpretation
range: boolean

HPO Phenotype Term
type: DatatypeProperty
comment: Human Phenotype Ontology term identifier, e.g. 'HP:0003002' (Breast carcinoma). Multiple HPO terms per patient or relative are expected.
range: string

Phenotype Onset Age
type: DatatypeProperty
comment: Age in years when the phenotype was first observed. Use HPO onset terms (HP:0011462 Young adult onset, etc.) when only categorical onset is known.
range: integer

Pedigree
type: Class
comment: A family pedigree: structured representation of relatives with conditions, ages of onset, and (where available) genotypes. Designed to round-trip with HL7 v3 Family History/Pedigree IG and FHIR FamilyMemberHistory while normalizing to Cascade's three-layer model.
subclass of: Entity

Pedigree Member
type: Class
comment: A single relative within a pedigree. Distinct from checkup:FamilyHistoryEntry, which is the patient-facing Layer 3 summary; PedigreeMember is the Layer 2 structured record carrying full HPO phenotype set, MONDO disease codes, age of onset/death, sex, and (optionally) carrier or affected status for specific variants.
subclass of: FamilyMemberHistory
subclass of: Entity

Proband
type: ObjectProperty
comment: The index patient — the family member who brought the family to clinical attention. Required on every Pedigree.
domain: Pedigree
range: Pedigree Member

Pedigree Member
type: ObjectProperty
comment: A relative included in the pedigree. Includes the proband.
domain: Pedigree
range: Pedigree Member

Relationship to Proband
type: ObjectProperty
comment: HL7 v3 RoleCode-aligned relationship, e.g. MTH (mother), FTH (father), SIS (sister), MGRMTH (maternal grandmother). Cardinal relations are first-class; complex relations expressed via nested PedigreeMember chains.
domain: Pedigree Member
range: Pedigree Relationship Role

Biological Sex
type: DatatypeProperty
comment: Biological sex of the relative as relevant to inheritance: 'male', 'female', 'unknown'. Distinct from gender identity, which is not modeled here.
domain: Pedigree Member
range: string

Deceased
type: DatatypeProperty
domain: Pedigree Member
range: boolean

Age at Death
type: DatatypeProperty
domain: Pedigree Member
range: integer

Carrier Status for Variant
type: ObjectProperty
comment: Tested status of this relative for a specific variant (typically the family's known pathogenic variant). Named-individual values: PositiveAffected, PositiveUnaffected, Negative, NotTested, Obligate.
domain: Pedigree Member
range: Carrier Status

Tested for Variant
type: ObjectProperty
comment: The specific Variant for which this relative's carrierStatus is reported. Allows a relative to have distinct statuses for different variants in the same family.
domain: Pedigree Member
range: Sequence Variant

Pathogenic
type: ACMG Classification
LOINC Answer Code Annotation: LA6668-3

Likely Pathogenic
type: ACMG Classification
LOINC Answer Code Annotation: LA26332-9

Uncertain Significance
type: ACMG Classification
LOINC Answer Code Annotation: LA26333-7

Likely Benign
type: ACMG Classification
LOINC Answer Code Annotation: LA26334-5

Benign
type: ACMG Classification
LOINC Answer Code Annotation: LA6675-8

Heterozygous
type: Zygosity Value

Homozygous
type: Zygosity Value

Hemizygous
type: Zygosity Value

Compound Heterozygous
type: Zygosity Value

Mosaic (low VAF)
type: Zygosity Value

Mosaic (high VAF)
type: Zygosity Value

Cis (same chromosome)
type: Allelic Phase Value

Trans (opposite chromosomes)
type: Allelic Phase Value

Phase Unknown
type: Allelic Phase Value

Autosomal Dominant
type: Mode of Inheritance

Autosomal Recessive
type: Mode of Inheritance

X-Linked Dominant
type: Mode of Inheritance

X-Linked Recessive
type: Mode of Inheritance

Mitochondrial
type: Mode of Inheritance

Y-Linked
type: Mode of Inheritance

Multifactorial / Polygenic
type: Mode of Inheritance

Unknown Inheritance
type: Mode of Inheritance

Monoallelic
type: Allelic Requirement

Biallelic
type: Allelic Requirement

Single Gene Test
type: Genetic Test Type

Gene Panel
type: Genetic Test Type

Whole Exome Sequencing
type: Genetic Test Type

Whole Genome Sequencing
type: Genetic Test Type

Chromosomal Microarray
type: Genetic Test Type

Karyotype
type: Genetic Test Type

MLPA
type: Genetic Test Type

Repeat Expansion Test
type: Genetic Test Type

Methylation Study
type: Genetic Test Type

RNA Sequencing
type: Genetic Test Type

Positive — Affected
type: Carrier Status

Positive — Unaffected
type: Carrier Status

Negative
type: Carrier Status

Not Tested
type: Carrier Status

Obligate Carrier
type: Carrier Status

Pending
type: Order Status

In Progress
type: Order Status

Resulted
type: Order Status

Cancelled
type: Order Status

Proband
type: Pedigree Relationship Role
comment: The index patient who brought the family to clinical attention. Marker, not a kinship relation.

Mother
type: Pedigree Relationship Role

Father
type: Pedigree Relationship Role

Sister
type: Pedigree Relationship Role

Brother
type: Pedigree Relationship Role

Daughter
type: Pedigree Relationship Role

Son
type: Pedigree Relationship Role

Maternal Aunt
type: Pedigree Relationship Role

Maternal Uncle
type: Pedigree Relationship Role

Paternal Aunt
type: Pedigree Relationship Role

Paternal Uncle
type: Pedigree Relationship Role

Maternal Grandmother
type: Pedigree Relationship Role

Maternal Grandfather
type: Pedigree Relationship Role

Paternal Grandmother
type: Pedigree Relationship Role

Paternal Grandfather
type: Pedigree Relationship Role

Maternal Cousin
type: Pedigree Relationship Role

Paternal Cousin
type: Pedigree Relationship Role

Niece
type: Pedigree Relationship Role

Nephew
type: Pedigree Relationship Role

Clinical Laboratory
type: Submitter Category

Consortium
type: Submitter Category
comment: Multi-institution curation consortium (e.g., ENIGMA for BRCA1/2).

Expert Panel
type: Submitter Category
comment: ClinGen Variant Curation Expert Panel (VCEP).

Research Group
type: Submitter Category

Single Clinician
type: Submitter Category

No Assertion Provided
type: Review Status
Star Rating: 0

Criteria Not Provided
type: Review Status
Star Rating: 0

Single Submitter (criteria provided)
type: Review Status
Star Rating: 1

Conflicting Submissions
type: Review Status
Star Rating: 1

Multiple Submitters, No Conflict
type: Review Status
Star Rating: 2

Expert Panel Reviewed
type: Review Status
Star Rating: 3

Practice Guideline
type: Review Status
Star Rating: 4

Causative
type: Causality Status
comment: This variant is the direct cause of the patient's phenotype.

Contributory
type: Causality Status
comment: This variant contributes to but is not solely responsible for the phenotype.

Uncertain Causality
type: Causality Status
comment: Causal role is unclear; further investigation needed.

Rejected
type: Causality Status
comment: This variant has been ruled out as the cause.

Germline
type: NamedIndividual
type: Somatic Status
comment: Variant present in the germline; inherited or de novo at conception; present in all cells of the individual.

Somatic
type: NamedIndividual
type: Somatic Status
comment: Variant acquired post-conception in a specific tissue / cell lineage; not heritable. Common in tumor samples.

Unknown Somatic Status
type: NamedIndividual
type: Somatic Status
comment: Origin not determined by the reporting workflow. Use when the source data is silent on germline-vs-somatic classification rather than guessing.

Short-read Illumina
type: Sequencing Technology
comment: Illumina short-read sequencing (NovaSeq, NextSeq, etc.). Dominant clinical platform.

Long-read Oxford Nanopore
type: Sequencing Technology
comment: Oxford Nanopore Technologies long-read sequencing (PromethION, MinION, etc.).

Long-read PacBio HiFi
type: Sequencing Technology
comment: Pacific Biosciences HiFi/CCS long-read sequencing (Revio, Sequel).

Mixed Technology
type: Sequencing Technology
comment: Combined short-read + long-read or hybrid sequencing strategies.

Genotyping Array
type: Sequencing Technology
comment: SNP genotyping array (Illumina Global Screening Array, Affymetrix Axiom, etc.). Used by 23andMe / AncestryDNA / MyHeritage / FTDNA — auto-tagged ConsumerGrade in the importer.

CLIA
type: Laboratory Certification
comment: Clinical Laboratory Improvement Amendments — US federal regulatory certification of clinical laboratories.

CAP
type: Laboratory Certification
comment: College of American Pathologists accreditation.

ISO 15189
type: Laboratory Certification
comment: ISO 15189 medical laboratory accreditation (international).

Uncertified
type: Laboratory Certification
comment: Laboratory holds no clinical certification (research lab, consumer DTC service).

BAM
type: File Format
comment: Binary Alignment/Map format. Cold tier (out-of-pod, referenced).

CRAM
type: File Format
comment: Compressed Reference-aligned Alignment/Map format. Cold tier.

FASTQ
type: File Format
comment: Raw sequencing reads with quality scores. Cold tier.

gVCF
type: File Format
comment: Genomic VCF — per-position records including reference-confidence blocks. Hot tier.

VCF
type: File Format
comment: Variant Call Format. Hot tier.

BCF
type: File Format
comment: Binary Call Format (binary VCF). Hot tier.

Other
type: File Format
comment: File format not enumerated above (e.g., methylation tracks, structural-variant-specific formats).

Consumer Array
type: Genomic Data Provenance
comment: Direct-to-consumer genotyping-array data (23andMe, AncestryDNA, MyHeritage, FTDNA). Phase 2C importer auto-tags every variant from this lane as genomics:ConsumerGrade with genomics:requiresConfirmation true on any pathogenic interpretation.

Clinical Sequencing
type: Genomic Data Provenance
comment: Clinical-grade sequencing performed by a CLIA/CAP/ISO15189-certified laboratory.

Research Sequencing
type: Genomic Data Provenance
comment: Research-quality sequencing without clinical certification (university cores, biobanks, research consortia).

Imported
type: Genomic Data Provenance
comment: Variant data imported from a third-party report, bundle, or pre-existing record where the original sequencing context is incomplete.

AI Extracted
type: Genomic Data Provenance
comment: Variant extracted by an LLM from unstructured narrative text (e.g., scanned PDF report). Treat as Imported provenance with elevated confirmation requirement.

Data Quality Tier
type: Class
comment: Tier classification of the quality of genomic data, used by the advisory engine to gate auto-applied recommendations and by narrative subsystems to drive disclosure language.

Clinical Grade
type: Data Quality Tier
comment: Sequencing performed by a CLIA-, CAP-, or ISO15189-certified laboratory using a clinical-grade method (>=30x mean coverage WGS, validated clinical panel, or equivalent), with raw files (BAM/CRAM/VCF) retained or accessible. The only tier from which Pathogenic / LikelyPathogenic interpretations may drive auto-applied care recommendations without confirmatory re-testing.

Research Grade
type: Data Quality Tier
comment: Research-quality sequencing without clinical certification — typical of university cores, biobanks, and research consortia. Adequate for hypothesis generation but requires confirmatory clinical-grade re-testing before driving care decisions.

Consumer Grade
type: Data Quality Tier
comment: Direct-to-consumer genotyping arrays (23andMe, AncestryDNA, MyHeritage, FTDNA) and consumer DTC sequencing without clinical certification. Genotyping arrays in particular interrogate only ~600k–900k SNP positions and have non-trivial false-positive rates for pathogenic variant calls. ALL Phase 2C consumer-array imports auto-tag this tier; Pathogenic / LikelyPathogenic interpretations on ConsumerGrade variants MUST carry requiresConfirmation true (SHACL-enforced).

Unknown Quality
type: Data Quality Tier
comment: Quality tier could not be determined from available metadata (no certification, coverage, or method information). Treated as ConsumerGrade by the downstream safety constraint — assume the worst until promoted.

LOINC Code Annotation
type: AnnotationProperty
comment: LOINC code or answer-list URI annotated on a property or named individual to record its Layer 1 standard mapping.

LOINC Answer Code Annotation
type: AnnotationProperty
comment: LOINC answer code (LA-prefixed string) for an enumerated value, e.g. LA6668-3 = Pathogenic.

ACMG Classification
type: Class

Zygosity Value
type: Class

Allelic Phase Value
type: Class

Mode of Inheritance
type: Class

Allelic Requirement
type: Class

Genetic Test Type
type: Class

Carrier Status
type: Class

Pedigree Relationship Role
type: Class

Order Status
type: Class

Submitter Category
type: Class

Review Status
type: Class

Causality Status
type: Class

Somatic Status
type: Class
comment: Closed enumeration of variant origin classifications (germline / somatic / unknown). Added in v1-draft.0.2.

Sequencing Technology
type: Class

Laboratory Certification
type: Class

File Format
type: Class

Genomic Data Provenance
type: Class

Phenotypic Observation
type: Class
comment: A single HPO-coded phenotypic feature observed in the index patient, captured outside the pedigree/variant context (e.g. during conversational phenotype intake). Supports negated findings (phenotype explicitly absent), essential for narrowing a differential. Provenance is typically cascade:SelfReported. Reuses genomics:hpoTerm for the HPO linkage.
version info: Added in genomics v1-draft.0.4

Phenotype Presence Value
type: Class
comment: Closed enumeration: whether the phenotype is present, absent, or resolved.
version info: Added in genomics v1-draft.0.4

Present
type: NamedIndividual
type: Phenotype Presence Value

Absent
type: NamedIndividual
type: Phenotype Presence Value
comment: Phenotype explicitly assessed and NOT present (negated finding).

Resolved
type: NamedIndividual
type: Phenotype Presence Value

Phenotype Presence
type: ObjectProperty
domain: Phenotypic Observation
range: Phenotype Presence Value
version info: Added in genomics v1-draft.0.4

Phenotype Onset Date
type: DatatypeProperty
comment: Calendar date the phenotype was first observed. Use genomics:phenotypeOnsetAge for age-based onset.
domain: Phenotypic Observation
range: date
version info: Added in genomics v1-draft.0.4

Phenotype Severity
type: DatatypeProperty
comment: Optional HPO severity modifier: mild, moderate, severe, profound (HP:0012823 modifier space).
domain: Phenotypic Observation
range: string
version info: Added in genomics v1-draft.0.4

Phenotype Note
type: DatatypeProperty
domain: Phenotypic Observation
range: string
version info: Added in genomics v1-draft.0.4