{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/b1baf39c-b1a3-4367-b6a6-c47152a2510b/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/CA025615/MONDO:0700269/097/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025615/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": "2026/7/15", "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/CA025615/MONDO:0700269/097/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA025615/MONDO:0700269/097/ci/CA025615/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 a SpliceAI score of 0.36 predicts an impact on splicing (score threshold >0.20). 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PMID: 31853058).", "contributionDate": { "date": "2026/7/15", "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": "CA025615/MONDO:0700269/097/ci/CA025615/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA025615/MONDO:0700269/097/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA025615/MONDO:0700269/097/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA025615/MONDO:0700269/097/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025615/MONDO:0700269/097/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025615/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": "2026/7/15", "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/CA025615/MONDO:0700269/097/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA025615/MONDO:0700269/097/ci/CA025615/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": "2026/7/15", "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": "CA025615/MONDO:0700269/097/ci/CA025615/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA025615/MONDO:0700269/097/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA025615/MONDO:0700269/097/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA025615/MONDO:0700269/097/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025615/MONDO:0700269/097/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025615/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": "2026/7/15", "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/CA025615/MONDO:0700269/097/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA025615/MONDO:0700269/097/ci/CA025615/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 and agarose gel electrophoresis demonstrated that the variant impacts splicing by exon 19 skipping (PMID: 32123317). The percent full-length and aberrant transcripts produced from the variant allele was not stated (PVS1 (RNA) and BP7_Strong (RNA) not met).", "contributionDate": { "date": "2026/7/15", "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": "CA025615/MONDO:0700269/097/ci/CA025615/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA025615/MONDO:0700269/097/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA025615/MONDO:0700269/097/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA025615/MONDO:0700269/097/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025615/MONDO:0700269/097/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025615/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": "2026/7/15", "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/CA025615/MONDO:0700269/097/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA025615/MONDO:0700269/097/ci/CA025615/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": "Missense variant predicted to alter splicing, functional data considered only from assays that measure effect via mRNA and protein. Reported by two calibrated studies incorporating mRNA splicing effect to exhibit function similar to pathogenic control variants (PMIDs: 39779857, 39779848). 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PMID: 31853058).", "contributionDate": { "date": "2026/7/15", "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": "CA025615/MONDO:0700269/097/ci/CA025615/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA025615/MONDO:0700269/097/0/1579/1581", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA025615/MONDO:0700269/097/1/1580", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA025615/MONDO:0700269/097/0/1579", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025615/MONDO:0700269/097/el/0/1654", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025615/MONDO:0700269/097/ei/1/1655", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2026/7/15", "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/CA025615/MONDO:0700269/097/el/0/1654/1656", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA025615/MONDO:0700269/097/ci/CA025615/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 and agarose gel electrophoresis demonstrated that the variant impacts splicing by exon 19 skipping (PMID: 32123317). The percent full-length and aberrant transcripts produced from the variant allele was not stated (PVS1 (RNA) and BP7_Strong (RNA) not met).", "contributionDate": { "date": "2026/7/15", "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": "CA025615/MONDO:0700269/097/ci/CA025615/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA025615/MONDO:0700269/097/0/1654/1656", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA025615/MONDO:0700269/097/1/1655", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA025615/MONDO:0700269/097/0/1654", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA025615/MONDO:0700269/097", "metadata": { "created": "2026-07-15T07:20:19.284Z", "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": "Wed, 15 Jul 2026 07:20:19 -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": "b1baf39c-b1a3-4367-b6a6-c47152a2510b", "variant": { "@id": "https://reg.genome.network/allele/CA025615", "id": "CAR:CA025615", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000059.4:c.8378G>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000059.4(BRCA2):c.8378G>T (p.Gly2793Val)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-27T10:22:52.671Z" } }, "status": { "code": 200, "name": "OK" } }