Variant Shape
Validation constraints for genomics:Variant. Enforces required gene-symbol identity, presence of at least one stable identifier across the four supported registries (CAid, VRS, ClinVar, dbSNP), and presence of a data-quality tier (used by the D-QUALITY-TIER safety constraint on downstream VariantInterpretations).
Gene Symbol
Recommended: genomics:geneSymbol (HGNC approved symbol, e.g., 'BRCA2'). Variant remains valid via stable identifiers (CAid/VRS/ClinVar/dbSNP) or VCF coordinates (refAllele+altAllele+genomicStartEnd) when source data lacks gene context.
Data Quality Tier
Variant must declare genomics:dataQualityTier as one of the four published genomics:DataQualityTier named individuals (ClinicalGrade, ResearchGrade, ConsumerGrade, UnknownQuality). Required so the D-QUALITY-TIER safety constraint on downstream VariantInterpretations can be evaluated.
ClinGen Allele Registry CAid
GA4GH VRS Identifier
ClinVar Variation ID
dbSNP rsID
Zygosity
genomics:zygosity is recommended; absence forces downstream tools to assume Heterozygous
Mosaicism Fraction (VAF)
genomics:mosaicismFraction, if present, must be an xsd:decimal between 0.0 and 1.0 inclusive (variant allele fraction)
Variant Allele Frequency
genomics:variantAlleleFrequency, if present, must be an xsd:decimal between 0.0 and 1.0 inclusive (fraction of reads supporting the alternate allele)
Reference Allele
Alternate Allele
Genomic Start-End Coordinates
Somatic Status
genomics:somaticStatus, if present, must be one of the three published genomics:SomaticStatus named individuals (Germline, Somatic, UnknownSomaticStatus)
Variant must carry at least one stable identifier among genomics:caId, genomics:vrsId, genomics:clinvarVariationId, or genomics:dbsnpRsId. HGVS strings alone are insufficient for reliable cross-database joins.
Variant Interpretation Shape
Validation constraints for genomics:VariantInterpretation. Implements D-Q5 (each Interpretation is per-(variant, condition); cardinality 1..1 on both genomics:variantInterpreted and genomics:condition) and D-QUALITY-TIER (the safety constraint on Pathogenic / LikelyPathogenic classifications).
Variant Interpreted
VariantInterpretation must reference exactly one Variant / CopyNumberVariant / Haplotype via genomics:variantInterpreted (D-Q5 — cardinality 1..1; multi-variant cases produce multiple Interpretation instances)
Associated Condition
VariantInterpretation must reference exactly one condition via genomics:condition (D-Q5 — cardinality 1..1; multi-condition cases produce multiple Interpretation instances, one per condition)
ACMG Classification
VariantInterpretation must declare genomics:acmgClassification as one of the five published genomics:AcmgClass named individuals (Pathogenic, LikelyPathogenic, VUS, LikelyBenign, Benign)
Review Status
genomics:reviewStatus, if present, must be one of the seven published genomics:ReviewStatus named individuals (NoAssertionProvided, CriteriaNotProvided, SingleSubmitter, ConflictingSubmissions, MultipleSubmittersNoConflict, ExpertPanelReviewed, PracticeGuideline). Recommended for advisory-engine trust weighting.
Requires Confirmation
genomics:requiresConfirmation, if present, must be a single xsd:boolean
Interpretation Date
genomics:interpretedDate (xsd:date) is recommended; needed for reclassification chronology
D-QUALITY-TIER safety constraint violated: this VariantInterpretation declares acmgClassification Pathogenic or LikelyPathogenic, but the referenced genomics:Variant is NOT genomics:ClinicalGrade tier AND genomics:requiresConfirmation is not true on this Interpretation. To resolve: EITHER promote the variant's genomics:dataQualityTier to genomics:ClinicalGrade (only valid if the underlying sequencing is CLIA/CAP/ISO15189-certified, >=30x coverage or validated panel-equivalent, with raw files retained), OR set genomics:requiresConfirmation true on this Interpretation. Consumer-grade pathogenic calls MUST NOT auto-apply care recommendations regardless of issuer trust.
Haplotype Shape
Validation constraints for genomics:Haplotype. The clinically actionable identifier in pharmacogenomics (PharmVar star alleles) and HLA typing is the star-allele symbol; this is required. Component variants are recommended for full provenance but optional in v1-draft.0.1.
Star Allele Symbol
Haplotype must carry exactly one non-empty genomics:starAlleleSymbol (PharmVar/HLA nomenclature, e.g. 'CYP2C19*2')
Component Variants
genomics:hasComponent is recommended; absence prevents downstream tools from auditing which constituent variants define this star allele. When present, each component must be a genomics:Variant or genomics:CopyNumberVariant.
Diplotype Shape
Validation constraints for genomics:Diplotype. A diplotype is, by definition, a pair of haplotypes — the ontology models this with two distinct properties (genomics:hapA, genomics:hapB) rather than a single 2..2 cardinality property. Each must be present exactly once.
Haplotype A
Diplotype must carry exactly one genomics:hapA referencing a genomics:Haplotype
Haplotype B
Diplotype must carry exactly one genomics:hapB referencing a genomics:Haplotype (a diplotype is by definition a pair of haplotypes)
Diplotype Notation
genomics:diplotypeNotation (e.g., '*1/*2') is recommended for direct matching against CPIC/DPWG guideline tables
Copy Number Variant Shape
Validation constraints specific to genomics:CopyNumberVariant. Applies VariantShape's constraints (geneSymbol, dataQualityTier, at least one stable ID) explicitly via sh:node, and adds the CNV-specific requirements: integer copy number, interval coordinates with reference.
Copy Number
CopyNumberVariant must carry exactly one genomics:copyNumber as a non-negative xsd:integer (0 = homozygous deletion, 1 = heterozygous deletion, 3+ = duplication/amplification)
CNV Interval Reference
CopyNumberVariant must carry exactly one genomics:cnvIntervalRef (reference contig name or accession, e.g., 'NC_000013.11')
CNV Interval Start
CopyNumberVariant must carry exactly one genomics:cnvIntervalStart as a positive xsd:integer (1-based, inclusive)
CNV Interval End
CopyNumberVariant must carry exactly one genomics:cnvIntervalEnd as a positive xsd:integer (1-based, inclusive)
Submitter Assertion Shape
Validation constraints for genomics:SubmitterAssertion (e.g., one ClinVar SCV record). Requires submitter identity and the asserted ACMG classification — these are what makes the assertion auditable. Note: the v1-draft.0.1 vocabulary does NOT define an assertionDate property nor a forward reference to the parent VariantInterpretation; the inverse link is genomics:aggregatedFrom (Interpretation→Assertion), which is the authoritative direction.
Submitter
SubmitterAssertion must carry exactly one non-empty genomics:submitter (lab/consortium/expert-panel name, e.g., 'ENIGMA', 'Ambry Genetics')
Asserted ACMG Classification
SubmitterAssertion must declare genomics:assertedClassification as one of the five published genomics:AcmgClass named individuals
SCV Accession
genomics:scvAccession is recommended for ClinVar-sourced submissions (audit trail to the original SCV record)
Submitter Category
genomics:submitterCategory is suggested; drives review-status weighting in the aggregate
Pedigree Shape
Validation constraints for genomics:Pedigree. A pedigree must have exactly one proband (the index patient who brought the family to attention) and at least one member (the proband counts).
Proband
Pedigree must reference exactly one genomics:proband (the index patient who brought the family to clinical attention)
Pedigree Members
Pedigree must reference at least one genomics:hasMember (the proband should be included)
Pedigree Member Shape
Validation constraints for genomics:PedigreeMember. The relationship-to-proband role is required and drawn from the closed HL7 v3 RoleCode-aligned named individuals declared in genomics.ttl.
Relationship Role
PedigreeMember must declare genomics:relativeRole as one of the published HL7 v3 RoleCode-aligned RelationshipRole named individuals (Proband, MTH, FTH, SIS, BRO, DAU, SON, MAUNT, MUNCLE, PAUNT, PUNCLE, MGRMTH, MGRFTH, PGRMTH, PGRFTH, MCOUSN, PCOUSN, NIECE, NEPHEW)
Biological Sex
genomics:relativeSex is recommended (one of 'male', 'female', 'unknown'); needed for X-linked / Y-linked inheritance reasoning
Carrier Status
genomics:carrierStatus, if present, must be one of the five published genomics:CarrierStatus named individuals (PositiveAffected, PositiveUnaffected, Negative, NotTested, Obligate)
Genetic Test Shape
Validation constraints for genomics:GeneticTest (FHIR DiagnosticReport-aligned). Requires test type. Note: testDate is not yet a declared property in v1-draft.0.1; chronology comes from prov:generatedAtTime.
Genetic Test Type
GeneticTest must declare genomics:testType as one of the ten published genomics:TestType named individuals (SingleGeneTest, GenePanelTest, ExomeSequencing, GenomeSequencing, ChromosomalMicroarray, KaryotypeAnalysis, MLPA, RepeatExpansionTest, MethylationStudy, RNASequencing)
Gene Panel
genomics:genePanel is recommended; the analytical scope distinguishes a clinically meaningful negative result from absence-of-evidence
Performing Laboratory
genomics:performingLab is recommended for provenance audit
Genetic Test Order Shape
Validation constraints for genomics:GeneticTestOrder (FHIR ServiceRequest-aligned). Requires order status (closed enumeration over the four OrderStatus named individuals) and order timestamp (genomics:orderedAt).
Order Status
GeneticTestOrder must declare genomics:orderStatus as one of the four published genomics:OrderStatus named individuals (OrderPending, OrderInProgress, OrderResulted, OrderCancelled)
Ordered At
GeneticTestOrder must carry exactly one genomics:orderedAt xsd:dateTime
Resulted In
genomics:resultedIn, if present, must reference exactly one genomics:GeneticTest. When orderStatus is OrderResulted, this link should be populated (conditional check lives in cascade-cli importer).
Sequencing Run Shape
Validation constraints for genomics:SequencingRun. Coverage depth, sequencing technology, and reference genome are required — these three drive the data-quality tier inference upstream of the D-QUALITY-TIER safety constraint. Laboratory certification is optional but, when present, must be one of the four published values.
Coverage Depth
SequencingRun must carry exactly one genomics:coverageDepth as a non-negative xsd:decimal (e.g., 30.0 for typical clinical WGS). Required for ClinicalGrade tier inference (>=30x WGS or validated panel-equivalent).
Sequencing Technology
SequencingRun must declare genomics:sequencingTechnology as one of the five published genomics:SequencingTechnology named individuals (ShortReadIllumina, LongReadONT, LongReadPacBio, Mixed, GenotypingArray). GenotypingArray auto-tags ConsumerGrade in the importer.
Laboratory Certification
genomics:laboratoryCertification, if present, must be one of the four published genomics:LaboratoryCertification named individuals (CLIA, CAP, ISO15189, Uncertified)
Variant Caller Version
genomics:variantCallerVersion is recommended (e.g., 'GATK 4.5.0', 'DeepVariant 1.6'); needed to distinguish caller-driven differences from biological ones
Sequencing Date
Raw File Shape
Validation constraints for genomics:RawFile pointer-and-hash records. Cascade does NOT ingest the bytes — only the manifest. Required: format (closed enum over seven FileFormat values), SHA-256 hash for integrity, opaque file location URI, and the reference genome the file is aligned against.
File Format
RawFile must declare genomics:fileFormat as one of the seven published genomics:FileFormat named individuals (BAM, CRAM, FASTQ, gVCF, VCF, BCF, OtherFileFormat). Hot tier (in-pod, encrypted): VCF/gVCF/BCF. Cold tier (out-of-pod, referenced): BAM/CRAM/FASTQ.
File SHA-256 Hash
RawFile must carry exactly one genomics:fileHashSHA256 as a 64-character lowercase hex SHA-256 digest. Required for byte-on-disk integrity verification.
File Location URI
RawFile must carry exactly one genomics:fileLocation xsd:anyURI (opaque pointer to where the bytes live: s3://, https://, file://, vendor-specific). Cascade does NOT validate or fetch this URI.
Reference Genome
RawFile must carry exactly one non-empty genomics:referenceGenome (e.g., 'GRCh38', 'GRCh37', 'T2T-CHM13'). Required for any downstream coordinate-based analysis.
File Size (Bytes)
genomics:fileSizeBytes, if present, must be a non-negative xsd:long (BAM/CRAM/FASTQ files routinely exceed 2^31 bytes)
htsget Endpoint
genomics:htsgetEndpoint is optional; when present, enables GA4GH htsget streaming of BAM/CRAM regions on demand