{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/d5362e38-f996-4ef0-b41b-c6bbcdbfb2b5/doc/sepio/version/1.2.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1528339111", "label": "ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GCK Version 1.3.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.3.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0015967", "id": "MONDO:0015967", "label": "monogenic diabetes", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA4239423/MONDO:0015967/086/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA4239423/MONDO:0015967/086/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2024/12/2", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA4239423/MONDO:0015967/086/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA4239423/MONDO:0015967/086/ci/CA4239423/MONDO:0015967/086.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "comments": "This variant was identified in two unrelated individuals with a clinical picture consistent with monogenic diabetes, however PS4_Moderate cannot be applied because this number is below the MDEP threshold (PMID: 12955723; PhD dissertation by Ovsyannikova).", "contributionDate": { "date": "2024/12/2", "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": "CA4239423/MONDO:0015967/086/ci/CA4239423/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA4239423/MONDO:0015967/086/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA4239423/MONDO:0015967/086/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA4239423/MONDO:0015967/086/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA4239423/MONDO:0015967/086/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA4239423/MONDO:0015967/086/ei/1/1595", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2024/12/2", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA4239423/MONDO:0015967/086/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA4239423/MONDO:0015967/086/ci/CA4239423/MONDO:0015967/086.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "comments": "This variant, located in biologically-relevant exon 9 of 10, is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 19790256). ", "contributionDate": { "date": "2024/12/2", "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": "CA4239423/MONDO:0015967/086/ci/CA4239423/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA4239423/MONDO:0015967/086/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA4239423/MONDO:0015967/086/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA4239423/MONDO:0015967/086/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA4239423/MONDO:0015967/086/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA4239423/MONDO:0015967/086/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2024/12/2", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA4239423/MONDO:0015967/086/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA4239423/MONDO:0015967/086/ci/CA4239423/MONDO:0015967/086.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "comments": "This variant has an incomputable gnomAD v2.1.1 Grpmax filtering allele frequency due to 1 copy in the European non-Finnish subpopulation and 0 copy in any other subpopulation, thereby meeting the ClinGen MDEP threshold criteria for PM2_Supporting (ENF Grpmax FAF <= 0.000003 and <= 2 copies in ENF and <=1 copy in any other subpopulation) (PM2_Supporting). \n gnomAD v4.0.0: Grpmax Filtering AF = 0; 1 case in ENF", "contributionDate": { "date": "2024/12/2", "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": "CA4239423/MONDO:0015967/086/ci/CA4239423/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA4239423/MONDO:0015967/086/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA4239423/MONDO:0015967/086/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA4239423/MONDO:0015967/086/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA4239423/MONDO:0015967/086/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA4239423/MONDO:0015967/086/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2024/12/2", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA4239423/MONDO:0015967/086/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA4239423/MONDO:0015967/086/ci/CA4239423/MONDO:0015967/086.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "comments": "This variant was identified in an individual with a phenotype suggestive of GCK-hyperglycemia; however, PP4 is unable to be evaluated due to insufficient clinical information (PMID: 12955723). This variant was identified in another individual with a phenotype suggestive of GCK-hyperglycemia, however the clinical parameters were not met for PP4 according to ClinGen MDEP VCEP (PhD dissertation by Ovsyannikova).", "contributionDate": { "date": "2024/12/2", "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": "CA4239423/MONDO:0015967/086/ci/CA4239423/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA4239423/MONDO:0015967/086/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA4239423/MONDO:0015967/086/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA4239423/MONDO:0015967/086/0/1633", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA4239423/MONDO:0015967/086", "metadata": { "created": "2024-12-20T22:32:54.387Z", "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, 20 Dec 2024 22:32:53 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.2.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "d5362e38-f996-4ef0-b41b-c6bbcdbfb2b5", "variant": { "@id": "https://reg.genome.network/allele/CA4239423", "id": "CAR:CA4239423", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_001354803.2:c.182C>A" } ], "preferred": true } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-05T16:17:26.016Z" } }, "status": { "code": 200, "name": "OK" } }