{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/df740ed6-94dd-4c52-bccb-3fcc306802e1/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/CA412745725/MONDO:0100437/106/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412745725/MONDO:0100437/106/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/9/7", "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/CA412745725/MONDO:0100437/106/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412745725/MONDO:0100437/106/ci/CA412745725/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 splicing impact predictor SpliceAI gives a score of 0.66 (donor loss), which is above the ClinGen X-linked IRD VCEP recommended threshold of ≥0.2 and predicts a damaging impact on splicing (PP3).", "contributionDate": { "date": "2025/9/7", "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": "CA412745725/MONDO:0100437/106/ci/CA412745725/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412745725/MONDO:0100437/106/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412745725/MONDO:0100437/106/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412745725/MONDO:0100437/106/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412745725/MONDO:0100437/106/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412745725/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": "2025/9/7", "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/CA412745725/MONDO:0100437/106/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412745725/MONDO:0100437/106/ci/CA412745725/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 diagnosis of retinitis pigmentosa with electroretinogram responses characteristic of rod-cone dystrophy (1 pt), genotyping by exome sequencing excluding an alternative basis for inherited retinal disease (2 pts), visual field changes (0.5 pts), and fundus abnormalities (0.5 pts), which together are specific for RPGR-related retinopathy (4 points, PMID: 33372982, PP4).", "contributionDate": { "date": "2025/9/7", "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": "CA412745725/MONDO:0100437/106/ci/CA412745725/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412745725/MONDO:0100437/106/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412745725/MONDO:0100437/106/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412745725/MONDO:0100437/106/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412745725/MONDO:0100437/106/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412745725/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": "2025/9/7", "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/CA412745725/MONDO:0100437/106/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412745725/MONDO:0100437/106/ci/CA412745725/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": "2025/9/7", "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": "CA412745725/MONDO:0100437/106/ci/CA412745725/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412745725/MONDO:0100437/106/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412745725/MONDO:0100437/106/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412745725/MONDO:0100437/106/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412745725/MONDO:0100437/106/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412745725/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": "2025/9/7", "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/CA412745725/MONDO:0100437/106/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412745725/MONDO:0100437/106/ci/CA412745725/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 6 apparently unrelated probands 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: 16969763, 22888088, 35432464, 36445968, 28559085, DOI 10.1055/s-0044-1779398, PS4_Strong). Other publications reported proband carrying this variant but failed to meet the requirements of the PS4 code (PMIDs: 34985506, 31213501, 37798099, 33372982).", "contributionDate": { "date": "2025/9/7", "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": "CA412745725/MONDO:0100437/106/ci/CA412745725/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412745725/MONDO:0100437/106/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412745725/MONDO:0100437/106/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412745725/MONDO:0100437/106/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412745725/MONDO:0100437/106/el/0/1648", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412745725/MONDO:0100437/106/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": "2025/9/7", "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/CA412745725/MONDO:0100437/106/el/0/1648/1650", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412745725/MONDO:0100437/106/ci/CA412745725/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 4 affected meioses from 2 families. (PP1_Strong; PMID: 22888088, DOI 10.1055/s-0044-1779398).", "contributionDate": { "date": "2025/9/7", "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": "CA412745725/MONDO:0100437/106/ci/CA412745725/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412745725/MONDO:0100437/106/0/1648/1650", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412745725/MONDO:0100437/106/1/1649", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412745725/MONDO:0100437/106/0/1648", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412745725/MONDO:0100437/106", "metadata": { "created": "2025-09-07T23:23:36.487Z", "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": "Sun, 07 Sep 2025 23:23:36 -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": "df740ed6-94dd-4c52-bccb-3fcc306802e1", "variant": { "@id": "https://reg.genome.network/allele/CA412745725", "id": "CAR:CA412745725", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_001034853.2:c.154G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_001034853.2(RPGR):c.154G>A (p.Gly52Arg)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-05T08:54:35.392Z" } }, "status": { "code": 200, "name": "OK" } }