{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/7f84a812-415f-4fa6-97d8-7c5d1e9c0664/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1570648177", "label": "ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RS1 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0010725", "id": "MONDO:0010725", "label": "X-linked retinoschisis", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412372934/MONDO:0010725/126/el/0/1648", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412372934/MONDO:0010725/126/ei/1/1649", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/5/20", "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/CA412372934/MONDO:0010725/126/el/0/1648/1650", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412372934/MONDO:0010725/126/ci/CA412372934/MONDO:0010725/126.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "The variant has been reported to segregate with retinal dystrophy through at least 3 meioses in the same family [proband, mother, grandfather, aunt, male cousin carry this variant- all males are affected]. (PP1_strong; PMID: 28060400).", "contributionDate": { "date": "2025/5/20", "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": "CA412372934/MONDO:0010725/126/ci/CA412372934/MONDO:0010725/126.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412372934/MONDO:0010725/126/0/1648/1650", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412372934/MONDO:0010725/126/1/1649", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412372934/MONDO:0010725/126/0/1648", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412372934/MONDO:0010725/126/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412372934/MONDO:0010725/126/ei/1/1832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/5/20", "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/CA412372934/MONDO:0010725/126/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412372934/MONDO:0010725/126/ci/CA412372934/MONDO:0010725/126.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "At least one proband harboring this variant exhibits a phenotype including appearance of schisis and reduced visual acuity before age 13 years and showing detachment, which together are highly specific for X-linked retinoschisis (PMID: 28060400, PP4_moderate).", "contributionDate": { "date": "2025/5/20", "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": "CA412372934/MONDO:0010725/126/ci/CA412372934/MONDO:0010725/126.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412372934/MONDO:0010725/126/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412372934/MONDO:0010725/126/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412372934/MONDO:0010725/126/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412372934/MONDO:0010725/126/el/0/1753", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412372934/MONDO:0010725/126/ei/1/1754", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/5/20", "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/CA412372934/MONDO:0010725/126/el/0/1753/1755", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412372934/MONDO:0010725/126/ci/CA412372934/MONDO:0010725/126.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.942, which is above the ClinGen X-linked IRD VCEP threshold of >0.932 and predicts a damaging effect on RS1 function (PP3_strong). The computational splicing predictor SpliceAI gives a delta score of 0.00 for all predictive splice changes, which is below the ClinGen X-linked IRD VCEP threshold of >0.2 and does not predict that the variant disrupts RS1 splicing.", "contributionDate": { "date": "2025/5/20", "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": "CA412372934/MONDO:0010725/126/ci/CA412372934/MONDO:0010725/126.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412372934/MONDO:0010725/126/0/1753/1755", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412372934/MONDO:0010725/126/1/1754", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412372934/MONDO:0010725/126/0/1753", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412372934/MONDO:0010725/126/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412372934/MONDO:0010725/126/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/5/20", "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/CA412372934/MONDO:0010725/126/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412372934/MONDO:0010725/126/ci/CA412372934/MONDO:0010725/126.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "This variant is absent from hemizygous individuals in gnomAD v4.1.0 (PM2_Supporting).", "contributionDate": { "date": "2025/5/20", "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": "CA412372934/MONDO:0010725/126/ci/CA412372934/MONDO:0010725/126.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412372934/MONDO:0010725/126/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412372934/MONDO:0010725/126/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412372934/MONDO:0010725/126/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412372934/MONDO:0010725/126", "metadata": { "created": "2025-05-20T16:50:56.967Z", "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": "Tue, 20 May 2025 16:50:56 -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": "7f84a812-415f-4fa6-97d8-7c5d1e9c0664", "variant": { "@id": "https://reg.genome.network/allele/CA412372934", "id": "CAR:CA412372934", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000330.4:c.227T>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000330.4(RS1):c.227T>A (p.Val76Asp)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-28T13:12:05.452Z" } }, "status": { "code": 200, "name": "OK" } }