{ "data": { "@context": "https://genboree.org/evrepo/api/context", "@id": "https://genboree.org/evrepo/api/summary/classification/e886266e-2f44-4bb3-96a0-eb3bfb13599b/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1566365955", "label": "ClinGen Leber Congenital Amaurosis/early onset Retinal Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RPE65 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0100368", "id": "MONDO:0100368", "label": "RPE65-related recessive retinopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA340748300/MONDO:0100368/120/el/0/1696", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA340748300/MONDO:0100368/120/ei/1/1697", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50082_EP170440666406958", "id": "CG-PCER-AGENT:CG_50082_EP170440666406958", "type": "Agent" }, "contributionDate": { "date": "2024/12/12", "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" } ], "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA340748300/MONDO:0100368/120/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA340748300/MONDO:0100368/120/ci/CA340748300/MONDO:0100368/120.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50082_EP170440666406958", "id": "CG-PCER-AGENT:CG_50082_EP170440666406958", "type": "Agent" }, "comments": "The variant exhibited 1.27% enzymatic activity in a retinoid isomerase assay relative to the wild-type control, which is lower than the ClinGen LCA / eoRD PS3_Supporting threshold of <10% activity, indicating that it triggers a severe defect in protein function (PS3_Supporting, PMID: 19431183).", "contributionDate": { "date": "2024/12/12", "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": "CA340748300/MONDO:0100368/120/ci/CA340748300/MONDO:0100368/120.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA340748300/MONDO:0100368/120/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA340748300/MONDO:0100368/120/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA340748300/MONDO:0100368/120/0/1696", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA340748300/MONDO:0100368/120/el/0/1636", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA340748300/MONDO:0100368/120/ei/1/1637", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50082_EP170440666406958", "id": "CG-PCER-AGENT:CG_50082_EP170440666406958", "type": "Agent" }, "contributionDate": { "date": "2024/12/12", "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" } ], "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA340748300/MONDO:0100368/120/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA340748300/MONDO:0100368/120/ci/CA340748300/MONDO:0100368/120.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50082_EP170440666406958", "id": "CG-PCER-AGENT:CG_50082_EP170440666406958", "type": "Agent" }, "comments": "This variant is present in gnomAD v.4.1.0 at a Grpmax allele frequency of 8.474e-7, with 1 / 1180026 alleles in the European (Non-Finnish) population, which is lower than the ClinGen LCA / eoRD VCEP PM2_Supporting threshold of <0.0002 (PM2_Supporting).", "contributionDate": { "date": "2024/12/12", "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": "CA340748300/MONDO:0100368/120/ci/CA340748300/MONDO:0100368/120.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA340748300/MONDO:0100368/120/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA340748300/MONDO:0100368/120/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA340748300/MONDO:0100368/120/0/1636", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA340748300/MONDO:0100368/120/el/0/1717", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA340748300/MONDO:0100368/120/ei/1/1718", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50082_EP170440666406958", "id": "CG-PCER-AGENT:CG_50082_EP170440666406958", "type": "Agent" }, "contributionDate": { "date": "2024/12/12", "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" } ], "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA340748300/MONDO:0100368/120/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA340748300/MONDO:0100368/120/ci/CA340748300/MONDO:0100368/120.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50082_EP170440666406958", "id": "CG-PCER-AGENT:CG_50082_EP170440666406958", "type": "Agent" }, "comments": "This variant has been reported in at least 1 proband with early-onset severe retinal dystrophy who was compound heterozygous with the c.271C>T p.Arg91Trp variant confirmed in trans by next-generation sequencing data (1 point, VCEP member-provided data), which was previously classified pathogenic by the ClinGen LCA / eoRD VCEP (1 total point, PM3).", "contributionDate": { "date": "2024/12/12", "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": "CA340748300/MONDO:0100368/120/ci/CA340748300/MONDO:0100368/120.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA340748300/MONDO:0100368/120/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA340748300/MONDO:0100368/120/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA340748300/MONDO:0100368/120/0/1717", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA340748300/MONDO:0100368/120/el/0/1690", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA340748300/MONDO:0100368/120/ei/1/1691", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50082_EP170440666406958", "id": "CG-PCER-AGENT:CG_50082_EP170440666406958", "type": "Agent" }, "contributionDate": { "date": "2024/12/12", "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" } ], "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA340748300/MONDO:0100368/120/el/0/1690/1692", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA340748300/MONDO:0100368/120/ci/CA340748300/MONDO:0100368/120.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50082_EP170440666406958", "id": "CG-PCER-AGENT:CG_50082_EP170440666406958", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.88, which is above the ClinGen LCA / eoRD VCEP threshold of ≥ 0.773 and predicts a damaging effect on RPE65 function (PP3_Moderate).", "contributionDate": { "date": "2024/12/12", "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": "CA340748300/MONDO:0100368/120/ci/CA340748300/MONDO:0100368/120.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA340748300/MONDO:0100368/120/0/1690/1692", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA340748300/MONDO:0100368/120/1/1691", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA340748300/MONDO:0100368/120/0/1690", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA340748300/MONDO:0100368/120", "metadata": { "created": "2024-12-12T18:44:54.076Z", "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": "Thu, 12 Dec 2024 18:44:53 -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": "e886266e-2f44-4bb3-96a0-eb3bfb13599b", "variant": { "@id": "https://reg.genome.network/allele/CA340748300", "id": "CAR:CA340748300", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000329.3:c.302C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000329.3(RPE65):c.302C>T (p.Thr101Ile)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://genboree.org/evrepo/api/summarysrvc", "when": "2026-04-11T09:06:31.861Z" } }, "status": { "code": 200, "name": "OK" } }