{ "data": [ { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/03de8501-996c-48bf-9d43-c794a465f00a/doc/sepio/version/2.1.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1530970787", "label": "ClinGen ENIGMA BRCA1 and BRCA2 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for BRCA1 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0700268", "id": "MONDO:0700268", "label": "BRCA1-related cancer predisposition", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0700268/092/el/0/1579", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0700268/092/ei/1/1580", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2025/5/23", "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/CA003230/MONDO:0700268/092/el/0/1579/1581", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003230/MONDO:0700268/092/ci/CA003230/MONDO:0700268/092.002", "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 0.48 (based on Family History LR=0.48), within the thresholds for supporting benign evidence (LR >0.23 & ≥0.48) (PMID: 31853058). The VCEP decided to not yet include BP5_Supporting as the LR is very close to the threshold of no evidence, and the Family history model is currently being updated. ", "contributionDate": { "date": "2025/5/23", "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": "CA003230/MONDO:0700268/092/ci/CA003230/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/0/1579/1581", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/1/1580", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/0/1579", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0700268/092/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0700268/092/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": "2025/5/23", "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/CA003230/MONDO:0700268/092/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003230/MONDO:0700268/092/ci/CA003230/MONDO:0700268/092.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "This BRCA1 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.386, above the recommended threshold of 0.28 for prediction of impact on BRCA1 function via protein change. SpliceAI predictor score of 0.02 suggests that the variant has no impact on splicing (score threshold <0.10) (PP3 met).", "contributionDate": { "date": "2025/5/23", "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": "CA003230/MONDO:0700268/092/ci/CA003230/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0700268/092/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0700268/092/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": "2025/5/23", "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/CA003230/MONDO:0700268/092/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003230/MONDO:0700268/092/ci/CA003230/MONDO:0700268/092.002", "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 v2.1 (exomes only, non-cancer subset, read depth ≥25) and gnomAD v3.1 (non-cancer subset, read depth ≥25) (PM2_Supporting met). ", "contributionDate": { "date": "2025/5/23", "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": "CA003230/MONDO:0700268/092/ci/CA003230/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0700268/092/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0700268/092/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": "2025/5/23", "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/CA003230/MONDO:0700268/092/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003230/MONDO:0700268/092/ci/EV000001593", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "Variant labelled as pathogenic", "contributionDate": { "date": "2025/5/23", "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": "CA003230/MONDO:0700268/092/ci/EV000001593", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/30765603", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA003230/MONDO:0700268/092/ci/EV000001592", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "Variant labelled as LOF", "contributionDate": { "date": "2025/5/23", "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": "CA003230/MONDO:0700268/092/ci/EV000001592", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/30209399", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/0/1828", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092", "metadata": { "created": "2025-05-30T21:59:31.608Z", "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, 30 May 2025 21:59:31 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "2.1.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "03de8501-996c-48bf-9d43-c794a465f00a", "variant": { "@id": "https://reg.genome.network/allele/CA003230", "id": "CAR:CA003230", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_007294.4:c.5090G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_007294.4(BRCA1):c.5090G>A (p.Cys1697Tyr)" } ], "type": "CAR" } }, { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/03de8501-996c-48bf-9d43-c794a465f00a/doc/sepio/version/2.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1530970787", "label": "ClinGen ENIGMA BRCA1 and BRCA2 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for BRCA1 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0700268", "id": "MONDO:0700268", "label": "BRCA1-related cancer predisposition", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0700268/092/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0700268/092/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": "2024/6/12", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0062", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0062", "label": "PP3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0700268/092/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003230/MONDO:0700268/092/ci/CA003230/MONDO:0700268/092.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "This BRCA1 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.386, above the recommended threshold of 0.28 for prediction of impact on BRCA1 function via protein change. SpliceAI predictor score of 0.02 suggests that the variant has no impact on splicing (score threshold <0.10) (PP3 met).", "contributionDate": { "date": "2024/6/12", "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": "CA003230/MONDO:0700268/092/ci/CA003230/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0700268/092/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0700268/092/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": "2024/6/12", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0030", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0030", "label": "PM2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0700268/092/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003230/MONDO:0700268/092/ci/CA003230/MONDO:0700268/092.002", "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 v2.1 (exomes only, non-cancer subset, read depth ≥25) and gnomAD v3.1 (non-cancer subset, read depth ≥25) (PM2_Supporting met). ", "contributionDate": { "date": "2024/6/12", "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": "CA003230/MONDO:0700268/092/ci/CA003230/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0700268/092/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0700268/092/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": "2024/6/12", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0052", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0052", "label": "PS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0700268/092/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003230/MONDO:0700268/092/ci/EV000001592", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "Variant labelled as LOF", "contributionDate": { "date": "2024/6/12", "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": "CA003230/MONDO:0700268/092/ci/EV000001592", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/30209399", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA003230/MONDO:0700268/092/ci/EV000001593", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "Variant labelled as pathogenic", "contributionDate": { "date": "2024/6/12", "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": "CA003230/MONDO:0700268/092/ci/EV000001593", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/30765603", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092/0/1828", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0700268/092", "metadata": { "created": "2024-09-28T04:44:11.933Z", "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": "Sat, 28 Sep 2024 04:44:11 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "2.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "03de8501-996c-48bf-9d43-c794a465f00a", "variant": { "@id": "https://reg.genome.network/allele/CA003230", "id": "CAR:CA003230", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_007294.4:c.5090G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_007294.4(BRCA1):c.5090G>A (p.Cys1697Tyr)" } ], "type": "CAR" } }, { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/03de8501-996c-48bf-9d43-c794a465f00a/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1530970787", "label": "ClinGen ENIGMA BRCA1 and BRCA2 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for BRCA1 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0011450", "id": "MONDO:0011450", "label": "breast-ovarian cancer, familial, susceptibility to, 1", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0011450/092/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0011450/092/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": "2023/10/8", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0052", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0052", "label": "PS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0011450/092/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003230/MONDO:0011450/092/ci/EV000001593", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "Variant labelled as pathogenic", "contributionDate": { "date": "2023/10/8", "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": "CA003230/MONDO:0011450/092/ci/EV000001593", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/30765603", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA003230/MONDO:0011450/092/ci/EV000001592", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "Variant labelled as LOF", "contributionDate": { "date": "2023/10/8", "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": "CA003230/MONDO:0011450/092/ci/EV000001592", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/30209399", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0011450/092/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0011450/092/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003230/MONDO:0011450/092/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0011450/092/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0011450/092/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": "2023/10/8", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0030", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0030", "label": "PM2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0011450/092/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003230/MONDO:0011450/092/ci/CA003230/MONDO:0011450/092.002", "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 v2.1 (exomes only, non-cancer subset, read depth ≥25) and gnomAD v3.1 (non-cancer subset, read depth ≥25) (PM2_Supporting met). ", "contributionDate": { "date": "2023/10/8", "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": "CA003230/MONDO:0011450/092/ci/CA003230/MONDO:0011450/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0011450/092/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0011450/092/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003230/MONDO:0011450/092/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0011450/092/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0011450/092/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": "2023/10/8", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0062", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0062", "label": "PP3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003230/MONDO:0011450/092/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003230/MONDO:0011450/092/ci/CA003230/MONDO:0011450/092.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "This BRCA1 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.386, above the recommended threshold of 0.28 for prediction of impact on BRCA1 function via protein change. SpliceAI predictor score of 0.02 suggests that the variant has no impact on splicing (score threshold <0.10) (PP3 met).", "contributionDate": { "date": "2023/10/8", "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": "CA003230/MONDO:0011450/092/ci/CA003230/MONDO:0011450/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0011450/092/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0011450/092/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003230/MONDO:0011450/092/0/1747", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003230/MONDO:0011450/092", "metadata": { "created": "2024-09-28T03:00:12.085Z", "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": "Sat, 28 Sep 2024 03:00:12 -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": "03de8501-996c-48bf-9d43-c794a465f00a", "variant": { "@id": "https://reg.genome.network/allele/CA003230", "id": "CAR:CA003230", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_007294.4:c.5090G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_007294.4(BRCA1):c.5090G>A (p.Cys1697Tyr)" } ], "type": "CAR" } } ], "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-13T20:14:59.946Z" } }, "status": { "code": 200, "name": "OK" } }