{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://erepo.genome.network/evrepo/api/summary/classification/7fb7723f-2d30-49a6-9690-e58f442e90a9/doc/sepio/version/1.2.1", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1529230095", "label": "ClinGen Severe Combined Immunodeficiency Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RMRP Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0009595", "id": "MONDO:0009595", "label": "cartilage-hair hypoplasia", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA257181/MONDO:0009595/088/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA257181/MONDO:0009595/088/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2025/12/9", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA257181/MONDO:0009595/088/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA257181/MONDO:0009595/088/ci/CA257181/MONDO:0009595/088.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "This variant is present in gnomAD v.4 at a Total allele frequency of 0.00003793, which is lower than the PM2_supporting threshold 0.0000447. while in the subgroup Finnish European, the allele frequency is 0.000552 [24/43478], which is higher than the threshold of 0.0000447. Therefore, the PM2_supporting was not met. NOTE: gnomAD does not provide GroupMax Filtering AF for this variant, therefore for this curation, we use the total allele frequency.", "contributionDate": { "date": "2025/12/9", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA257181/MONDO:0009595/088/ci/CA257181/MONDO:0009595/088.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA257181/MONDO:0009595/088/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA257181/MONDO:0009595/088/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA257181/MONDO:0009595/088/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA257181/MONDO:0009595/088/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA257181/MONDO:0009595/088/ei/1/1679", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2025/12/9", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA257181/MONDO:0009595/088/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA257181/MONDO:0009595/088/ci/CA257181/MONDO:0009595/088.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "A multiple-case family with this variant in trans with n.70A>C is reported with two affected siblings. Therefore this criterion is met at default strength. ", "contributionDate": { "date": "2025/12/9", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA257181/MONDO:0009595/088/ci/CA257181/MONDO:0009595/088.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA257181/MONDO:0009595/088/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA257181/MONDO:0009595/088/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA257181/MONDO:0009595/088/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA257181/MONDO:0009595/088/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA257181/MONDO:0009595/088/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2025/12/9", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA257181/MONDO:0009595/088/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA257181/MONDO:0009595/088/ci/CA257181/MONDO:0009595/088.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "At least one patient presented Methapyseal dysplasia (+1.0 points) and hypotrichosis (+0.5 points) and therefore this criterion is met at default strength (PMID: 11207361). ", "contributionDate": { "date": "2025/12/9", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA257181/MONDO:0009595/088/ci/CA257181/MONDO:0009595/088.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA257181/MONDO:0009595/088/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA257181/MONDO:0009595/088/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA257181/MONDO:0009595/088/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA257181/MONDO:0009595/088/el/0/1669", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA257181/MONDO:0009595/088/ei/1/1670", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2025/12/9", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA257181/MONDO:0009595/088/el/0/1669/1671", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA257181/MONDO:0009595/088/ci/CA257181/MONDO:0009595/088.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "This variant is reported in trans with the variant (70A>g) in 6 patients (+1.0 points each). The total score is 6 meeting this criterion PM3_VeryStrong. PMID: 11207361 ", "contributionDate": { "date": "2025/12/9", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA257181/MONDO:0009595/088/ci/CA257181/MONDO:0009595/088.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA257181/MONDO:0009595/088/0/1669/1671", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA257181/MONDO:0009595/088/1/1670", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA257181/MONDO:0009595/088/0/1669", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA257181/MONDO:0009595/088", "metadata": { "created": "2026-03-24T21:59:44.475Z", "note": "DISCLAIMER: While the data/content in this document is approved by ClinGen expert panel(s), the SEPIO schema presented here is an initial prototype and has not been reviewed nor finalized by the ClinGen Data Exchange Modeling Team. We expect it to differ significantly from the final schema.", "producedAtUTC": "Tue, 24 Mar 2026 21:59:44 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.2.1" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "7fb7723f-2d30-49a6-9690-e58f442e90a9", "variant": { "@id": "https://reg.genome.network/allele/CA257181", "id": "CAR:CA257181", "relatedContextualAllele": [ { "alleleName": [ { "name": "NR_003051.4:n.264G>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NR_003051.4(RMRP):n.264G>T" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-05-15T02:15:07.345Z" } }, "status": { "code": 200, "name": "OK" } }