{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/bb4fcf01-da35-40c3-ad54-1f3a33abe2d6/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 1.2.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.2.0" }, "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/CA021531/MONDO:0700269/097/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA021531/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/CA021531/MONDO:0700269/097/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA021531/MONDO:0700269/097/ci/CA021531/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 with patient-derived mRNA demonstrated that the variant impacts splicing by skipping of exon 6 and skipping of exon 5 and 6 (both out of frame). Confirmation with a minigene assay showed no full-length transcript to be produced by the variant allele, using a semi-quantitative assessment with gel electrophoresis, cloning and sequence analysis (PMID: 19267246). RT-PCRSeq confirmed the aberrant transcripts and reported that no full-length transcript was produced by the variant allele (Ambry internal data). Appropriate code strength determined by comparison of results to PVS1 decision tree (PVS1 (RNA)).", "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": "CA021531/MONDO:0700269/097/ci/CA021531/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA021531/MONDO:0700269/097/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA021531/MONDO:0700269/097/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA021531/MONDO:0700269/097/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA021531/MONDO:0700269/097/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA021531/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/CA021531/MONDO:0700269/097/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA021531/MONDO:0700269/097/ci/CA021531/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 synonymous (silent) variant has a SpliceAI score of 0.84, predicting an impact on splicing (score threshold ≥0.2) (PP3 not applied because a PVS1 code is met).\n", "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": "CA021531/MONDO:0700269/097/ci/CA021531/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA021531/MONDO:0700269/097/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA021531/MONDO:0700269/097/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA021531/MONDO:0700269/097/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA021531/MONDO:0700269/097/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA021531/MONDO:0700269/097/ei/1/1634", "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/CA021531/MONDO:0700269/097/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA021531/MONDO:0700269/097/ci/CA021531/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": "Multifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 0.92 (based on Co-occurrence LR=1.05; Family History LR=0.88), which is above the ENIGMA BRCA1/2 VCEP threshold for BP5 (>0.48) and below PP4 (<2.08) (BP5 and PP4 not met; PMID: 31853058.\n", "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": "CA021531/MONDO:0700269/097/ci/CA021531/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA021531/MONDO:0700269/097/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA021531/MONDO:0700269/097/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA021531/MONDO:0700269/097/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA021531/MONDO:0700269/097/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA021531/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/CA021531/MONDO:0700269/097/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA021531/MONDO:0700269/097/ci/CA021531/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": "CA021531/MONDO:0700269/097/ci/CA021531/MONDO:0700269/097.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA021531/MONDO:0700269/097/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA021531/MONDO:0700269/097/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA021531/MONDO:0700269/097/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA021531/MONDO:0700269/097", "metadata": { "created": "2026-07-15T07:23:41.372Z", "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 07:23:39 -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": "bb4fcf01-da35-40c3-ad54-1f3a33abe2d6", "variant": { "@id": "https://reg.genome.network/allele/CA021531", "id": "CAR:CA021531", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000059.4:c.516G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000059.4(BRCA2):c.516G>A (p.Lys172=)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-15T20:05:23.102Z" } }, "status": { "code": 200, "name": "OK" } }