{ "data": { "@context": "https://genboree.org/evrepo/api/context", "@id": "https://genboree.org/evrepo/api/summary/classification/fb3934fe-b004-493d-ac6a-987127cebac3/doc/sepio/version/1.0.0", "assertionMethod": { "type": "VariantPathogenicityInterpretationGuideline" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0021060", "id": "MONDO:0021060", "label": "RASopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA273745/MONDO:0021060/004/el/0/1798", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA273745/MONDO:0021060/004/ei/1/1799", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/7/1", "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/0011", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0011", "label": "PM2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA273745/MONDO:0021060/004/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA273745/MONDO:0021060/004/ci/CA273745/MONDO:0021060/004.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "Absent from both versions of gnomAD.", "contributionDate": { "date": "2020/7/1", "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": "CA273745/MONDO:0021060/004/ci/CA273745/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA273745/MONDO:0021060/004/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA273745/MONDO:0021060/004/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA273745/MONDO:0021060/004/0/1798", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA273745/MONDO:0021060/004/el/0/1837", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA273745/MONDO:0021060/004/ei/1/1838", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/7/1", "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/0061", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0061", "label": "PP2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA273745/MONDO:0021060/004/el/0/1837/1839", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA273745/MONDO:0021060/004/ci/CA273745/MONDO:0021060/004.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "The variant is located in the RAF1 gene, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants and pathogenic missense variants are common (PP2; 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PMID 29493581).", "contributionDate": { "date": "2020/7/1", "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": "CA273745/MONDO:0021060/004/ci/EV000000212", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/29493581", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA273745/MONDO:0021060/004/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA273745/MONDO:0021060/004/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA273745/MONDO:0021060/004/0/1615", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA273745/MONDO:0021060/004/el/0/1780", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA273745/MONDO:0021060/004/ei/1/1781", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/7/1", "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/008", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "008", "label": "PM5", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA273745/MONDO:0021060/004/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA273745/MONDO:0021060/004/ci/CA273745/MONDO:0021060/004.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "PM5 not applied since PM1 is already met.", "contributionDate": { "date": "2020/7/1", "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": "CA273745/MONDO:0021060/004/ci/CA273745/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA273745/MONDO:0021060/004/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA273745/MONDO:0021060/004/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA273745/MONDO:0021060/004/0/1780", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA273745/MONDO:0021060/004/el/0/1735", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA273745/MONDO:0021060/004/ei/1/1736", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/7/1", "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/0053", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0053", "label": "PS4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA273745/MONDO:0021060/004/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA273745/MONDO:0021060/004/ci/CA273745/MONDO:0021060/004.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "Identified in 6 independent occurrences in patients with a RASopathy (PS4; PMID: 30732632, 31560489, 31145547; Partners Laboratory for Molecular Medicine, Institute of Human Genetics, Otto von Guericke University Magdeburg internal data; ClinVar SCV000061370.6).", "contributionDate": { "date": "2020/7/1", "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": "CA273745/MONDO:0021060/004/ci/CA273745/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA273745/MONDO:0021060/004/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA273745/MONDO:0021060/004/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA273745/MONDO:0021060/004/0/1735", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA273745/MONDO:0021060/004", "metadata": { "created": "2024-09-23T16:54:55.255Z", "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": "Mon, 23 Sep 2024 16:54:55 -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": "fb3934fe-b004-493d-ac6a-987127cebac3", "variant": { "@id": "https://reg.genome.network/allele/CA273745", "id": "CAR:CA273745", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_002880.3:c.788T>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_002880.3(RAF1):c.788T>G (p.Val263Gly)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://genboree.org/evrepo/api/summarysrvc", "when": "2026-06-06T03:11:57.201Z" } }, "status": { "code": 200, "name": "OK" } }