{ "data": { "@context": "https://genboree.org/evrepo/api/context", "@id": "https://genboree.org/evrepo/api/summary/classification/702b812f-014e-492b-88c7-b2b4632cd24c/doc/sepio/version/1.1.0", "assertionMethod": { "type": "VariantPathogenicityInterpretationGuideline" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0015967", "id": "MONDO:0015967", "label": "monogenic diabetes", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA386960848/MONDO:0015967/017/el/0/1594", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA386960848/MONDO:0015967/017/ei/1/1595", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50016_EP163553329359758", "id": "CG-PCER-AGENT:CG_50016_EP163553329359758", "type": "Agent" }, "contributionDate": { "date": "2023/12/2", "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/0017", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000220", "id": "SEPIO:0000220", "label": "Pathogenic Very Strong" }, "id": "0017", "label": "PVS1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA386960848/MONDO:0015967/017/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA386960848/MONDO:0015967/017/ci/CA386960848/MONDO:0015967/017.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50016_EP163553329359758", "id": "CG-PCER-AGENT:CG_50016_EP163553329359758", "type": "Agent" }, "comments": "This variant is predicted to cause loss of part exon 2, leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).", "contributionDate": { "date": "2023/12/2", "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": "CA386960848/MONDO:0015967/017/ci/CA386960848/MONDO:0015967/017.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA386960848/MONDO:0015967/017/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA386960848/MONDO:0015967/017/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA386960848/MONDO:0015967/017/0/1594", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA386960848/MONDO:0015967/017/el/0/1630", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA386960848/MONDO:0015967/017/ei/1/1631", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50016_EP163553329359758", "id": "CG-PCER-AGENT:CG_50016_EP163553329359758", "type": "Agent" }, "contributionDate": { "date": "2023/12/2", "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/0040", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0040", "label": "PP1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA386960848/MONDO:0015967/017/el/0/1630/1632", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA386960848/MONDO:0015967/017/ci/CA386960848/MONDO:0015967/017.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50016_EP163553329359758", "id": "CG-PCER-AGENT:CG_50016_EP163553329359758", "type": "Agent" }, "comments": "This variant segregated with diabetes, with three informative meioses in three families (PP1_Moderate; internal lab contributors). 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"id": "0036", "label": "PS1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA386960848/MONDO:0015967/017/el/0/1744/1746", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA386960848/MONDO:0015967/017/ci/CA386960848/MONDO:0015967/017.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50016_EP163553329359758", "id": "CG-PCER-AGENT:CG_50016_EP163553329359758", "type": "Agent" }, "comments": "The HNF1A(NM_000545.8):c.526+1G>A variant at the same canonical nucleotide has been classified as pathogenic for monogenic diabetes by the ClinGen MDEP, and c.526+1G>C has a similar predicted impact by Splice AI (donor loss 100% and donor gain at -33 bp 64% vs. 65%) (PS1_Supporting).", "contributionDate": { "date": "2023/12/2", "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": "CA386960848/MONDO:0015967/017/ci/CA386960848/MONDO:0015967/017.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA386960848/MONDO:0015967/017/0/1744/1746", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA386960848/MONDO:0015967/017/1/1745", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA386960848/MONDO:0015967/017/0/1744", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA386960848/MONDO:0015967/017/el/0/1633", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA386960848/MONDO:0015967/017/ei/1/1634", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50016_EP163553329359758", "id": "CG-PCER-AGENT:CG_50016_EP163553329359758", "type": "Agent" }, "contributionDate": { "date": 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history highly specific for HNF1A-MODY (MODY probability calculator result >50%, negative genetic testing for HNF4A) (PP4).", "contributionDate": { "date": "2023/12/2", "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": "CA386960848/MONDO:0015967/017/ci/CA386960848/MONDO:0015967/017.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA386960848/MONDO:0015967/017/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA386960848/MONDO:0015967/017/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA386960848/MONDO:0015967/017/0/1633", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA386960848/MONDO:0015967/017/el/0/1735", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA386960848/MONDO:0015967/017/ei/1/1736", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50016_EP163553329359758", "id": "CG-PCER-AGENT:CG_50016_EP163553329359758", "type": "Agent" }, "contributionDate": { "date": "2023/12/2", "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/CA386960848/MONDO:0015967/017/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA386960848/MONDO:0015967/017/ci/CA386960848/MONDO:0015967/017.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50016_EP163553329359758", "id": "CG-PCER-AGENT:CG_50016_EP163553329359758", "type": "Agent" }, "comments": "This variant was identified in 9 unrelated individuals with non-autoimmune and non-absolute/near-absolute insulin-deficient diabetes (PS4).", "contributionDate": { "date": "2023/12/2", "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": "CA386960848/MONDO:0015967/017/ci/CA386960848/MONDO:0015967/017.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA386960848/MONDO:0015967/017/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA386960848/MONDO:0015967/017/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA386960848/MONDO:0015967/017/0/1735", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA386960848/MONDO:0015967/017", "metadata": { "created": "2024-09-23T21:40:39.448Z", "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 21:40:39 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.1.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "702b812f-014e-492b-88c7-b2b4632cd24c", "variant": { "@id": "https://reg.genome.network/allele/CA386960848", "id": "CAR:CA386960848", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000545.8:c.526+1G>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000545.8(HNF1A):c.526+1G>C" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://genboree.org/evrepo/api/summarysrvc", "when": "2026-04-11T10:36:10.923Z" } }, "status": { "code": 200, "name": "OK" } }