{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/1ec84574-6253-4687-af4b-51eb058a0e23/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1552193476", "label": "ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RPGR Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0100437", "id": "MONDO:0100437", "label": "RPGR-related retinopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA270037/MONDO:0100437/106/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA270037/MONDO:0100437/106/ei/1/1829", "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/CA270037/MONDO:0100437/106/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA270037/MONDO:0100437/106/ci/EV000001827", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "Gerasimavicius et al. tried to predict variant effects by protein structural information and molecular mechanisms. This variant was tested as well.", "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": "CA270037/MONDO:0100437/106/ci/EV000001827", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/32958805", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA270037/MONDO:0100437/106/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA270037/MONDO:0100437/106/ei/1/1736", "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/CA270037/MONDO:0100437/106/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA270037/MONDO:0100437/106/ci/CA270037/MONDO:0100437/106.002", "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 has been reported in at least 1 proband meeting the PS4 requirement of some functional vision impairment in affected males by age 30, with decreased or absent cone and/or rod ERG responses (PMIDs: 25324289, 26316687, 26427425). Since all three papers have reported the same family, PS4_Supporting was not met.", "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": "CA270037/MONDO:0100437/106/ci/CA270037/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA270037/MONDO:0100437/106/el/0/1690", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA270037/MONDO:0100437/106/ei/1/1691", "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/CA270037/MONDO:0100437/106/el/0/1690/1692", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA270037/MONDO:0100437/106/ci/CA270037/MONDO:0100437/106.002", "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 0.904, which is between the ClinGen X-linked IRD VCEP threshold of 0.773 to 0.931 and predicts a damaging effect on RPGR function (PP3_moderate). The computational splicing predictor SpliceAI gives a delta score of 0.01 for acceptor gain, which is below the ClinGen X-linked IRD VCEP threshold of >0.2 and does not predict that the variant disrupts RPGR 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": "CA270037/MONDO:0100437/106/ci/CA270037/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/0/1690/1692", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/1/1691", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/0/1690", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA270037/MONDO:0100437/106/el/0/1630", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA270037/MONDO:0100437/106/ei/1/1631", "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/CA270037/MONDO:0100437/106/el/0/1630/1632", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA270037/MONDO:0100437/106/ci/CA270037/MONDO:0100437/106.002", "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 affected\nmeioses from 1 family. (PP1; PMID: [26316687, 25324289]).", "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": "CA270037/MONDO:0100437/106/ci/CA270037/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/0/1630/1632", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/1/1631", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/0/1630", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA270037/MONDO:0100437/106/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA270037/MONDO:0100437/106/ei/1/1634", "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/CA270037/MONDO:0100437/106/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA270037/MONDO:0100437/106/ci/CA270037/MONDO:0100437/106.002", "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 early onset (1 pt) of night blindness (0.5 pts), decreased central vision acuity (0.5 pts), visual field constriction (0.5 pts), family history consistent with X-linked inheritance (2 pts), delayed or milder phenotype in females (1 pt), and next-generation sequencing-based genotyping identifying no alternative causes of retinal disease (2 pts), which together are specific for RPGR-related recessive retinopathy (7.5 pts, PP4, PMID: 25324289).", "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": "CA270037/MONDO:0100437/106/ci/CA270037/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA270037/MONDO:0100437/106/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA270037/MONDO:0100437/106/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/CA270037/MONDO:0100437/106/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA270037/MONDO:0100437/106/ci/CA270037/MONDO:0100437/106.002", "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": "CA270037/MONDO:0100437/106/ci/CA270037/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA270037/MONDO:0100437/106", "metadata": { "created": "2025-05-20T20:36:11.909Z", "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 20:36:11 -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": "1ec84574-6253-4687-af4b-51eb058a0e23", "variant": { "@id": "https://reg.genome.network/allele/CA270037", "id": "CAR:CA270037", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_001034853.2:c.922G>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_001034853.2(RPGR):c.922G>C (p.Ala308Pro)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-28T23:48:53.440Z" } }, "status": { "code": 200, "name": "OK" } }