{ id: "acmgv4-vp-example-101", type: "Statement", # Formal type in the model is 'Statement' proposition: { # a Proposition object captures the possible fact assessed by the Statement, using a subject, predicate, object, qualifier (SPOQ) semantic modeling pattern. id: "ex:Proposition001", # the proposition here is that "NM_004700.4:c.803CCT[1] is causal for AD nonsyndromic hearing loss 2A" type: "VariantPathogenicityProposition", subjectVariant: "clingen.ar:CA347424", # 'subjectVariant' specializes the VA Core 'subject' attribute, and holds a CatVRS 'Categorical Variant' whose full representtion is not shown here. predicate: "isCausalFor", # the predicate for this Statement profile is fixed at 'isCausalFor' objectCondition: { # 'objectCondition' specialilzes the VA Core 'object' attribute. id: "mondo:0010817", # this is a MappableConcept object that represents the Condition, using names/codes from existing code systems conceptType: "Disease", name: "Autosomal dominant nonsyndromic hearing loss 2A", # the name for the concept as assigned by the data provider primaryCoding: { # holds a Coding object, where the concept is defined in the 'code' or 'name' field code: "C2677637", # the code from the MedGen terminology for AD nonsyndromic hearing loss 2A system: "https://www.ncbi.nlm.nih.gov/medgen/", iris: [ "http://identifiers.org/medgen/C2677637" ] } }, penetranceQualifier: { # holds a MappableConcept that reports qualifying penetrance information about the object condition (here, that the statement holds for high penetrance AD hearing loss) primaryCoding: { code: "high", system: "ga4gh-gks-term:pathogenicity-penetrance-qualifier", # code system here is a locally defined placeholder, until we formalize terminological standards for use in the VA-Spec }, name: "high" }, geneContextQualifier: { # holds a MappableConcept that reports qualifying gene information about the subject variant (here, that the statement holds for the gene MYO15A) primaryCoding: { code: "9132", system: "http://identifiers.org/ncbigene/", iris: [ "http://identifiers.org/ncbigene/9132", "https://www.ncbi.nlm.nih.gov/gene/9132" ], name: "KCNQ4" } }, modeOfInheritanceQualifier: { # holds a MappableConcept that reports qualifying inheritance information about the object condition (here, that the statement holds for autosomal dominant inheritance) primaryCoding: { code: "HP:0000006", system: "https://identifiers.org/", # code system here is a locally defined placeholder, until we formalize terminological standards for use in the VA-Spec iris: [ "https://identifiers.org/HP:0000006", "https://hpo.jax.org/browse/term/HP:0000006" ] }, name: "Autosomal dominant inheritance" }, alleleOriginQualifier: { # holds a MappableConcept that reports qualifying allele information about the subject variant (here, that the statement holds for germline variants) primaryCoding: { code: "germline", system: "ga4gh-gks-term:pathogenicity-allele-origin-qualifier", # code system here is a locally defined placeholder, until we formalize terminological standards for use in the VA-Spec }, name: "germline" } }, direction: "supports", # an enumerated string that indicates the Statement 'supports' the Proposition as true strength: { # holds a MappableConcept reporting that confidence/evidence for this stated support primaryCoding: { code: "definitive", # the code here is a term based on language used in the ACMG guidleines, as ACMG does not provide a formal code system for this system: "ACMG Guidelines v4" } }, score: 16.0, # a numeric score that indicates the strength of evidence for the Statement classification: { # holds a MappableConcept reporting the final ACMG classification of the subject variant to be 'pathogneic' primaryCoding: { code: "pathogenic", # the code here is a term based on language in the ACMG guidelines, as ACMG does not provide a formal code system for this system: "ACMG Guidelines v4" } }, contributions: [ { # a list of Contribution objects, each describing how an agent contributed to the Statement type: "Contribution", contributor: { # reports who made this contribution id: "clinvar.submitter/500139", type: "Agent", name: "ClinVar Staff, National Center for Biotechnology Information (NCBI)" }, activityType: "evaluator role", # reports the type of contribution that was made (here an evaluation activity) date: 2015-08-20 # reports when this contribution was performed }, { # a second Contribution object, describing a different contribution to the Statement type: "Contribution", contributor: { # reports who made this contribution id: "clinvar.submitter/500139", type: "Agent", name: "ClinVar Staff, National Center for Biotechnology Information (NCBI)" }, activityType: "submitter role", # reports the type of contribution that was made (here a submission activity) date: 2018-06-12 # reports when this contribution was performed } ], specifiedBy: { # holds a Method object describing guidelines followed in generating the knowledge reported in the Statement type: "Method", reportedIn: { # a document that describes the Method (this is all we are given about this Method in the source data) type: "Document", name: "ACMG Guidelines v4" } }, hasEvidenceLines: [ # a list of EvidenceLine objects, each describing a piece of evidence that supports the Statement { type: "EvidenceLine", # Human Observation EvidenceLine id: "human-observation", # a unique identifier for this EvidenceLine directionOfEvidenceProvided: "supports", # an enumerated string that indicates the EvidenceLine 'supports' the Statement as true strengthOfEvidenceProvided: { # holds a MappableConcept reporting that confidence/evidence for this stated support primaryCoding: { code: "definitive", # the code here is a term based on language used in the ACMG guidleines, as ACMG does not provide a formal code system for this system: "ACMG Guidelines v4" } }, scoreOfEvidenceProvided: 9.0, # a numeric score that indicates the strength of evidence for this EvidenceLine evidenceLineCode: "HO", # I Think we really need something like this!! specifiedBy: { # It would be very nice to have the ability to put a unique IRI to the specific RULE used by this evidence line. type: "Method", name: "ACMG v4 evidence cap score summation method", # a name for the Method, this could be a code to represent the various rules used in the ACMG guidelines methodType: "algorithm", # a type of Method, used to further sub-categorize methods. Should be a controlled vocabulary possibly defined in the VA-Spec? description: "All ACMG v4 evidence cap score summation is performed by summing the final score from the child evidence lines and then capped if it exceeds the cap and rounded down if it is fractional." # a description of the Method # cspec-entry-value-rule-iri = "cspec:HO-Rule" # rule type = sum, cap and round rule # min cap = -? # max cap = 25 # round = true }, hasEvidenceLines: [ { type: "EvidenceLine", # Observation Counting EvidenceLine id: "observation-counting", directionOfEvidenceProvided: "supports", strengthOfEvidenceProvided: { primaryCoding: { code: "definitive", system: "ACMG Guidelines v4" } }, finalScoreOfEvidenceProvided: 5.0, # we have discussed allowing users to edit this score and capture a note if so. rawScoreOfEvidenceProvided: 5.0, evidenceLineCode: "HO.ObsCnt", # I Think we really need something like this!! specifiedBy: { type: "Method", name: "ACMG v4 evidence cap score summation method", methodType: "Algorigthm", description: "All ACMG v4 evidence cap score summation is performed by summing the final score from the child evidence lines and then capped if it exceeds the cap and rounded down if it is fractional." # a description of the Method }, hasEvidenceLines: [ { type: "EvidenceLine", # Population Frequency EvidenceLine id: "obs_pop", directionOfEvidenceProvided: "neutral", strengthOfEvidenceProvided: { # AByrne's comment: it's not clear that strength is relevant at any EvidenceLine Level. primaryCoding: { code: "uncertain", system: "ACMG Guidelines v4" } }, scoreOfEvidenceProvided: 0.0, evidenceLineCode: "HO.ObsCnt.PopFreq", # I Think we really need something like this!! specifiedBy: { type: "Method", name: "", methodType: "Algorigthm", description: "All ACMG v4 evidence cap score summation is performed by summing the final score from the child evidence lines and then capped if it exceeds the cap and rounded down if it is fractional." # a description of the Method }, hasEvidenceLines: [ { type: "EvidenceLine", # Population Frequency EvidenceLine id: "obs_pop", directionOfEvidenceProvided: "neutral", strengthOfEvidenceProvided: { # AByrne's comment: it's not clear that strength is relevant at any EvidenceLine Level. primaryCoding: { code: "uncertain", system: "ACMG Guidelines v4" } }, scoreOfEvidenceProvided: 0.0, evidenceLineCode: "HO.ObsCnt.PopFreq.MAF", # I Think we really need something like this!! hasEvidenceItems: [ { type: "EvidenceItem", itemType: "DAF", id: "daf-threshold-for-this-case", value: 0.0001 }, { type: "EvidenceItem", itemType: "CohortAlleleFrequenceFAF", id: "caf-001", value: 0.000000034 } ] }, { #homozyogotes evidence line score } ] }, { type: "EvidenceLine", # Affected Observations EvidenceLine id: "obs_aff", directionOfEvidenceProvided: "supports", strengthOfEvidenceProvided: { primaryCoding: { code: "definitive", system: "ACMG Guidelines v4" } }, scoreOfEvidenceProvided: 5.5, specifiedBy: { type: "Method", name: "ACMG v4 evidence cap score summation method", methodType: "Algorigthm", description: "All ACMG v4 evidence cap score summation is performed by summing the final score from the child evidence lines and then capped if it exceeds the cap and rounded down if it is fractional." # a description of the Method }, hasEvidenceLines: [ { type: "EvidenceLine", # Affecteds-Monoallelic EvidenceLine id: "obs_aff_monoallelic", directionOfEvidenceProvided: "supports", strengthOfEvidenceProvided: { # likely primaryCoding: { code: "likely", system: "ACMG Guidelines v4" } }, scoreOfEvidenceProvided: 2.5, specifiedBy: { type: "Method", name: "ACMG v4 evidence cap score summation method", methodType: "Algorigthm", description: "All ACMG v4 evidence cap score summation is performed by summing the final score from the child evidence lines and then capped if it exceeds the cap and rounded down if it is fractional." # a description of the Method } }, { type: "EvidenceLine", # Affecteds-De novo EvidenceLine id: "obs_aff_denovo", directionOfEvidenceProvided: "supports", strengthOfEvidenceProvided: { # likely primaryCoding: { code: "likely", system: "ACMG Guidelines v4" } }, scoreOfEvidenceProvided: 3.0, specifiedBy: { type: "Method", name: "ACMG v4 evidence cap score summation method", methodType: "Algorigthm", description: "All ACMG v4 evidence cap score summation is performed by summing the final score from the child evidence lines and then capped if it exceeds the cap and rounded down if it is fractional." # a description of the Method } } ] } ] }, { type: "EvidenceLine", # Locus Specificity EvidenceLine id: "locus-specificity", directionOfEvidenceProvided: "supports", strengthOfEvidenceProvided: { primaryCoding: { code: "definitive", # the code here is a term based on language used in the ACMG guidleines, as ACMG does not provide a formal code system for this system: "ACMG Guidelines v4" } }, scoreOfEvidenceProvided: 4.0, specifiedBy: { type: "Method", name: "ACMG v4 evidence cap score summation method", # a name for the Method, this could be a code to represent the various rules used in the ACMG guidelines methodType: "Algorigthm", # a type of Method, used to further sub-categorize methods. Should be a controlled vocabulary possibly defined in the VA-Spec? description: "All ACMG v4 evidence cap score summation is performed by summing the final score from the child evidence lines and then capped if it exceeds the cap and rounded down if it is fractional." # a description of the Method } } ] }, { # a second EvidenceLine object Func & Predictive Data EvidenceLine type: "EvidenceLine", id: "predictive-and-functional-data", # a unique identifier for this EvidenceLine directionOfEvidenceProvided: "supports", # an enumerated string that indicates the EvidenceLine 'supports' the Statement as true strengthOfEvidenceProvided: { # holds a MappableConcept reporting that confidence/evidence for this stated support primaryCoding: { code: "definitive", # the code here is a term based on language used in the ACMG guidleines, as ACMG does not provide a formal code system for this system: "ACMG Guidelines v4" } }, scoreOfEvidenceProvided: 7.0, # a numeric score that indicates the strength of evidence for this EvidenceLine evidenceLineCode: "FP", specifiedBy: { type: "Method", name: "ACMG v4 evidence cap score summation method", # a name for the Method, this could be a code to represent the various rules used in the ACMG guidelines methodType: "Algorigthm", # a type of Method, used to further sub-categorize methods. Should be a controlled vocabulary possibly defined in the VA-Spec? description: "All ACMG v4 evidence cap score summation is performed by summing the final score from the child evidence lines and then capped if it exceeds the cap and rounded down if it is fractional." # a description of the Method }, hasEvidenceLines: [ # a list of EvidenceLine objects, each describing a piece of evidence that supports the EvidenceLine { # an EvidenceLine object type: "EvidenceLine", id: "functional-data", # a unique identifier for this EvidenceLine directionOfEvidenceProvided: "supports", # an enumerated string that indicates the EvidenceLine 'supports' the Statement as true strengthOfEvidenceProvided: { # holds a MappableConcept reporting that confidence/evidence for this stated support primaryCoding: { code: "definitive", # the code here is a term based on language used in the ACMG guidleines, as ACMG does not provide a formal code system for this system: "ACMG Guidelines v4" } }, scoreOfEvidenceProvided: 7.0, # a numeric score that indicates the strength of evidence for this EvidenceLine specifiedBy: { type: "Method", name: "ACMG v4 evidence cap score summation method", # a name for the Method, this could be a code to represent the various rules used in the ACMG guidelines methodType: "Algorigthm", # a type of Method, used to further sub-categorize methods. Should be a controlled vocabulary possibly defined in the VA-Spec? description: "All ACMG v4 evidence cap score summation is performed by summing the final score from the child evidence lines and then capped if it exceeds the cap and rounded down if it is fractional." # a description of the Method }, } ] } ] }