{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/fc216372-ccef-4b6f-9a3a-5bfaaee6eb7b/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1535438831", "label": "ClinGen ENIGMA BRCA1 and BRCA2 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for BRCA2 Version 1.1.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.1.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0700269", "id": "MONDO:0700269", "label": "BRCA2-related cancer predisposition", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1139663040/MONDO:0700269/097/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1139663040/MONDO:0700269/097/ei/1/1595", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2025/8/24", "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/CA1139663040/MONDO:0700269/097/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA1139663040/MONDO:0700269/097/ci/CA1139663040/MONDO:0700269/097.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "This variant is reported to result in aberrant mRNA splicing. RT-PCR demonstrated that the variant impacts splicing by partial exon skipping (PMID: 24395671). The percent reference (full-length) and aberrant transcripts produced from the variant allele assessed using gel electrophoresis was not stated. Final code strength determined by the rubric: PVS1_N/A (RNA).", "contributionDate": { "date": "2025/8/24", "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": "CA1139663040/MONDO:0700269/097/ci/CA1139663040/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1139663040/MONDO:0700269/097/el/0/1777", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1139663040/MONDO:0700269/097/ei/1/1778", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2025/8/24", "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/CA1139663040/MONDO:0700269/097/el/0/1777/1779", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA1139663040/MONDO:0700269/097/ci/CA1139663040/MONDO:0700269/097.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "This variant was not observed in gnomAD v2.1 (exomes only, non-cancer subset) or gnomAD v3.1 (non-cancer subset) but is not meeting the specified read depths threshold ≥20 (PM2_Supporting, BS1, and BA1 are not met).", "contributionDate": { "date": "2025/8/24", "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": "CA1139663040/MONDO:0700269/097/ci/CA1139663040/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/0/1777/1779", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/1/1778", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/0/1777", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1139663040/MONDO:0700269/097/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1139663040/MONDO:0700269/097/ei/1/1829", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2025/8/24", "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/CA1139663040/MONDO:0700269/097/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA1139663040/MONDO:0700269/097/ci/CA1139663040/MONDO:0700269/097.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "Intronic variant, functional data considered only from assays that measure effect via mRNA and protein. Reported by one calibrated study incorporating mRNA splicing effects to exhibit protein function similar to pathogenic control variants (PMID:24395671) (PS3 met).", "contributionDate": { "date": "2025/8/24", "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": "CA1139663040/MONDO:0700269/097/ci/CA1139663040/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1139663040/MONDO:0700269/097/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1139663040/MONDO:0700269/097/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2025/8/24", "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/CA1139663040/MONDO:0700269/097/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA1139663040/MONDO:0700269/097/ci/CA1139663040/MONDO:0700269/097.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "This variant is absent from gnomAD v4.1 (read depth ≥25) (PM2_Supporting met).\n\n", "contributionDate": { "date": "2025/8/24", "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": "CA1139663040/MONDO:0700269/097/ci/CA1139663040/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1139663040/MONDO:0700269/097/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1139663040/MONDO:0700269/097/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2025/8/24", "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/CA1139663040/MONDO:0700269/097/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA1139663040/MONDO:0700269/097/ci/CA1139663040/MONDO:0700269/097.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "This variant has been detected in one individual with phenotype consistent with BRCA2-Fanconi Anemia (FA). At least one clinical feature of FA (physical features, pathology findings and cancer diagnosis ≤5yr) and confirmed chromosome breakage are seen in this individual. They were compound heterozygous for the variant and a pathogenic or likely pathogenic variant confirmed to be in trans. Total points equated to 2 (PM3 met; PMIDs: 12065746, 12750298, 24395671, 26183081).", "contributionDate": { "date": "2025/8/24", "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": "CA1139663040/MONDO:0700269/097/ci/CA1139663040/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1139663040/MONDO:0700269/097/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1139663040/MONDO:0700269/097/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2025/8/24", "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/CA1139663040/MONDO:0700269/097/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA1139663040/MONDO:0700269/097/ci/CA1139663040/MONDO:0700269/097.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "This variant was not observed in gnomAD v2.1 (exomes only, non-cancer subset) or gnomAD v3.1 (non-cancer subset) but is not meeting the specified read depths threshold ≥20 (PM2_Supporting, BS1, and BA1 are not met).", "contributionDate": { "date": "2025/8/24", "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": "CA1139663040/MONDO:0700269/097/ci/CA1139663040/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097/0/1804", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA1139663040/MONDO:0700269/097", "metadata": { "created": "2025-08-24T22:50:21.308Z", "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": "Sun, 24 Aug 2025 22:50:21 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "fc216372-ccef-4b6f-9a3a-5bfaaee6eb7b", "variant": { "@id": "https://reg.genome.network/allele/CA1139663040", "id": "CAR:CA1139663040", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000059.4:c.-40+1G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000059.4(BRCA2):c.-40+1G>A" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-29T15:26:52.645Z" } }, "status": { "code": 200, "name": "OK" } }