{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/3b78f2f4-c9a2-4f6c-a699-d8b0931557ed/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 1.2", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.2" }, "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/CA387746014/MONDO:0700269/097/el/0/1738", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA387746014/MONDO:0700269/097/ei/1/1739", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2026/7/24", "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/CA387746014/MONDO:0700269/097/el/0/1738/1740", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA387746014/MONDO:0700269/097/ci/CA387746014/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": "at Very strong level:\nMultifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 2273.3 (based on Cosegregation LR=1733.4; Pathology LR=4.86; Family History LR=0.27), above the thresholds for very strong evidence towards pathogenicity (LR >350) (PP4_Very strong met; PMID: 34597585, 31131967, Internal lab contributor). ", "contributionDate": { "date": "2026/7/24", "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": "CA387746014/MONDO:0700269/097/ci/CA387746014/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA387746014/MONDO:0700269/097/0/1738/1740", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA387746014/MONDO:0700269/097/1/1739", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA387746014/MONDO:0700269/097/0/1738", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA387746014/MONDO:0700269/097/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA387746014/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": "2026/7/24", "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/CA387746014/MONDO:0700269/097/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA387746014/MONDO:0700269/097/ci/CA387746014/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": "Reported by three calibrated studies to exhibit protein function similar to pathogenic control variants (PMIDs: 38417439, 39779857, 39779848) (PS3 met).", "contributionDate": { "date": "2026/7/24", "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": "CA387746014/MONDO:0700269/097/ci/CA387746014/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA387746014/MONDO:0700269/097/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA387746014/MONDO:0700269/097/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA387746014/MONDO:0700269/097/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA387746014/MONDO:0700269/097/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA387746014/MONDO:0700269/097/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2026/7/24", "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/CA387746014/MONDO:0700269/097/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA387746014/MONDO:0700269/097/ci/CA387746014/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 BRCA2 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.45, above the recommended threshold of 0.30 for prediction of impact on BRCA2 function via protein change. A SpliceAI score of 0.15 indicates an unclear predicted impact on splicing (score threshold 0.10-0.20) (PP3 met).", "contributionDate": { "date": "2026/7/24", "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": "CA387746014/MONDO:0700269/097/ci/CA387746014/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA387746014/MONDO:0700269/097/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA387746014/MONDO:0700269/097/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA387746014/MONDO:0700269/097/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA387746014/MONDO:0700269/097/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA387746014/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": "2026/7/24", "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/CA387746014/MONDO:0700269/097/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA387746014/MONDO:0700269/097/ci/CA387746014/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 ≥25x in >90% samples, PM2_Supporting met).", "contributionDate": { "date": "2026/7/24", "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": "CA387746014/MONDO:0700269/097/ci/CA387746014/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA387746014/MONDO:0700269/097/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA387746014/MONDO:0700269/097/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA387746014/MONDO:0700269/097/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA387746014/MONDO:0700269/097", "metadata": { "created": "2026-07-24T03:55:39.401Z", "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": "Fri, 24 Jul 2026 03:55:39 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "3b78f2f4-c9a2-4f6c-a699-d8b0931557ed", "variant": { "@id": "https://reg.genome.network/allele/CA387746014", "id": "CAR:CA387746014", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000059.4:c.7787G>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000059.4(BRCA2):c.7787G>T (p.Gly2596Val)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-27T10:48:21.449Z" } }, "status": { "code": 200, "name": "OK" } }