{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/fd9da888-326a-4e5f-9568-3d06139dae7e/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/CA412744915/MONDO:0100437/106/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412744915/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": "2025/9/8", "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/CA412744915/MONDO:0100437/106/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412744915/MONDO:0100437/106/ci/EV000001872", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "Injection of human RPGR mRNA harboring the variant into zebrafish embryos rescued ciliary defects such as hydrocephaly / edema / kinked tail associated with rpgr silencing (Figure 4B).", "contributionDate": { "date": "2025/9/8", "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": "CA412744915/MONDO:0100437/106/ci/EV000001872", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/19815619", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412744915/MONDO:0100437/106/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412744915/MONDO:0100437/106/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/9/8", "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/CA412744915/MONDO:0100437/106/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412744915/MONDO:0100437/106/ci/CA412744915/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": "Another missense variant in the same codon, NM_001034853.2(RPGR):c.494G>A (p.Gly165Asp) has been classified as pathogenic for RPGR-related retinopathy by the ClinGen X-linked IRD VCEP, while no benign missense variants have been identified in this codon. The present variant has a higher Grantham’s distance (109) than the comparison variant (94), and SpliceAI has been used to confirm that neither variant has a predicted impact on RPGR splicing (PM5_Supporting). ", "contributionDate": { "date": "2025/9/8", "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": "CA412744915/MONDO:0100437/106/ci/CA412744915/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412744915/MONDO:0100437/106/el/0/1588", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412744915/MONDO:0100437/106/ei/1/1589", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/9/8", "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/CA412744915/MONDO:0100437/106/el/0/1588/1590", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412744915/MONDO:0100437/106/ci/EV000001872", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "Injection of human RPGR mRNA harboring the variant into zebrafish embryos rescued ciliary defects such as hydrocephaly / edema / kinked tail associated with rpgr silencing (Figure 4B).", "contributionDate": { "date": "2025/9/8", "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": "CA412744915/MONDO:0100437/106/ci/EV000001872", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/19815619", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/0/1588/1590", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/1/1589", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/0/1588", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412744915/MONDO:0100437/106/el/0/1753", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412744915/MONDO:0100437/106/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": "2025/9/8", "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/CA412744915/MONDO:0100437/106/el/0/1753/1755", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412744915/MONDO:0100437/106/ci/CA412744915/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 0.982, which is above the ClinGen X-linked IRD VCEP threshold of ≥ 0.932 and predicts a damaging effect on RPGR function (PP3_Strong). The splicing predictor SpliceAI gives a delta score of 0.06 for splice donor loss, which is lower than the threshold of >0.5 and does not strongly predict a disruption of splicing.", "contributionDate": { "date": "2025/9/8", "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": "CA412744915/MONDO:0100437/106/ci/CA412744915/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/0/1753/1755", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/1/1754", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/0/1753", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412744915/MONDO:0100437/106/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412744915/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": "2025/9/8", "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/CA412744915/MONDO:0100437/106/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412744915/MONDO:0100437/106/ci/CA412744915/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 with early-onset severe retinal dystrophy fulfilling the requirements of onset before the age of 30 and abnormalities on ERG. Because phenotypes were absent other than the next generation sequencing-based genotyping excluding alternative causes in other loci (2 pts), this criterion is not met.", "contributionDate": { "date": "2025/9/8", "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": "CA412744915/MONDO:0100437/106/ci/CA412744915/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412744915/MONDO:0100437/106/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412744915/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": "2025/9/8", "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/CA412744915/MONDO:0100437/106/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412744915/MONDO:0100437/106/ci/CA412744915/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 gnomAD v4.1.0 (PM2_Supporting).", "contributionDate": { "date": "2025/9/8", "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": "CA412744915/MONDO:0100437/106/ci/CA412744915/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412744915/MONDO:0100437/106/el/0/1606", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412744915/MONDO:0100437/106/ei/1/1607", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/9/8", "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/CA412744915/MONDO:0100437/106/el/0/1606/1608", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412744915/MONDO:0100437/106/ci/CA412744915/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 2 apparently unrelated probands meeting one of the PS4 requirements of a male with some functional vision impairment by age 30 and/or decreased or absent ERG responses, or a female with functional visual abnormality and documentation of a male relative affected with retinitis pigmentosa (PMIDs: 34745198, 31630094, PS4_Supporting). ", "contributionDate": { "date": "2025/9/8", "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": "CA412744915/MONDO:0100437/106/ci/CA412744915/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/0/1606/1608", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/1/1607", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106/0/1606", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412744915/MONDO:0100437/106", "metadata": { "created": "2025-09-08T00:45:45.249Z", "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": "Mon, 08 Sep 2025 00:45:44 -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": "fd9da888-326a-4e5f-9568-3d06139dae7e", "variant": { "@id": "https://reg.genome.network/allele/CA412744915", "id": "CAR:CA412744915", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_001034853.2:c.494G>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_001034853.2(RPGR):c.494G>T (p.Gly165Val)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-04T23:31:15.324Z" } }, "status": { "code": 200, "name": "OK" } }