{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/53cb3135-d743-49c8-bb7f-db0b047108e7/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1733815116", "label": "ClinGen Leber Congenital Amaurosis/early onset Retinal Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GUCY2D Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0100453", "id": "MONDO:0100453", "label": "GUCY2D-related recessive retinopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA915949552/MONDO:0100453/167/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA915949552/MONDO:0100453/167/ei/1/1595", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2025/1/30", "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/CA915949552/MONDO:0100453/167/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA915949552/MONDO:0100453/167/ci/CA915949552/MONDO:0100453/167.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "comments": "This is a frameshift variant that introduces a premature stop codon into exon 4 of 20, and is predicted to lead to nonsense-mediated decay in a gene in which loss-of-function is an established mechanism of disease (PVS1).", "contributionDate": { "date": "2025/1/30", "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": "CA915949552/MONDO:0100453/167/ci/CA915949552/MONDO:0100453/167.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA915949552/MONDO:0100453/167/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA915949552/MONDO:0100453/167/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA915949552/MONDO:0100453/167/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA915949552/MONDO:0100453/167/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA915949552/MONDO:0100453/167/ei/1/1679", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2025/1/30", "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/CA915949552/MONDO:0100453/167/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA915949552/MONDO:0100453/167/ci/CA915949552/MONDO:0100453/167.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "comments": "The variant has been reported to segregate with LCA through the proband plus 1 similarly affected relative, with the variant present in the compound heterozygous state (PP1; PMID: 32865313).\n", "contributionDate": { "date": "2025/1/30", "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": "CA915949552/MONDO:0100453/167/ci/CA915949552/MONDO:0100453/167.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA915949552/MONDO:0100453/167/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA915949552/MONDO:0100453/167/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA915949552/MONDO:0100453/167/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA915949552/MONDO:0100453/167/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA915949552/MONDO:0100453/167/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2025/1/30", "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/CA915949552/MONDO:0100453/167/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA915949552/MONDO:0100453/167/ci/CA915949552/MONDO:0100453/167.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "comments": "At least one proband harboring this variant exhibits a phenotype including a diagnosis of LCA/eoRD (0.5pts), previous genetic testing that did not provide an alternative explanation for visual impairment (2 pts), symptomatic onset between birth and 5 years (1 pt), nystagmus (1 pt), decreased peripheral vision (1 pt), and decreased central vision (1 pt) which together are specific for GUCY2D-related recessive retinopathy (6.5 total points, PMID: 32865313, PP4).\n", "contributionDate": { "date": "2025/1/30", "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": "CA915949552/MONDO:0100453/167/ci/CA915949552/MONDO:0100453/167.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA915949552/MONDO:0100453/167/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA915949552/MONDO:0100453/167/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA915949552/MONDO:0100453/167/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA915949552/MONDO:0100453/167/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA915949552/MONDO:0100453/167/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2025/1/30", "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/CA915949552/MONDO:0100453/167/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA915949552/MONDO:0100453/167/ci/CA915949552/MONDO:0100453/167.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "comments": "This variant is absent from gnomAD v. 4.1.0 (PM2_Supporting).", "contributionDate": { "date": "2025/1/30", "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": "CA915949552/MONDO:0100453/167/ci/CA915949552/MONDO:0100453/167.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA915949552/MONDO:0100453/167/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA915949552/MONDO:0100453/167/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA915949552/MONDO:0100453/167/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA915949552/MONDO:0100453/167", "metadata": { "created": "2025-01-30T18:55:49.855Z", "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, 30 Jan 2025 18:55:49 -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": "53cb3135-d743-49c8-bb7f-db0b047108e7", "variant": { "@id": "https://reg.genome.network/allele/CA915949552", "id": "CAR:CA915949552", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000180.4:c.1245del" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000180.4(GUCY2D):c.1245del (p.Phe415fs)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-02T04:13:51.626Z" } }, "status": { "code": 200, "name": "OK" } }