{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/eeb69d61-f36f-44f5-bf81-a8d89de0be61/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1567863456", "label": "ClinGen Severe Combined Immunodeficiency Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RAG2 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0000573", "id": "MONDO:0000573", "label": "recombinase activating gene 2 deficiency", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA380142798/MONDO:0000573/124/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA380142798/MONDO:0000573/124/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2024/5/14", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0063", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0063", "label": "PP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA380142798/MONDO:0000573/124/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA380142798/MONDO:0000573/124/ci/CA380142798/MONDO:0000573/124.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "One patient was reported at Invitae carrying this variant - with no clinical features described; Not possible to evaluate for PP4.", "contributionDate": { "date": "2024/5/14", "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": "CA380142798/MONDO:0000573/124/ci/CA380142798/MONDO:0000573/124.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA380142798/MONDO:0000573/124/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA380142798/MONDO:0000573/124/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA380142798/MONDO:0000573/124/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA380142798/MONDO:0000573/124/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA380142798/MONDO:0000573/124/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2024/5/14", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0030", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0030", "label": "PM2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA380142798/MONDO:0000573/124/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA380142798/MONDO:0000573/124/ci/CA380142798/MONDO:0000573/124.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "The highest population minor allele frequency in gnomAD v4 is 0.0001941 (1/5152 alleles) in the Ashkenazi Jewish population. As this is a known bottleneck population, it will not be considered here for PM2_Supporting. As no other alleles have been reported in other populations, PM2 at the supporting level is applied (Absence in GnomAD).", "contributionDate": { "date": "2024/5/14", "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": "CA380142798/MONDO:0000573/124/ci/CA380142798/MONDO:0000573/124.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA380142798/MONDO:0000573/124/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA380142798/MONDO:0000573/124/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA380142798/MONDO:0000573/124/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA380142798/MONDO:0000573/124/el/0/1681", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA380142798/MONDO:0000573/124/ei/1/1682", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2024/5/14", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0054", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0054", "label": "PM1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA380142798/MONDO:0000573/124/el/0/1681/1683", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA380142798/MONDO:0000573/124/ci/CA380142798/MONDO:0000573/124.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "This variant is located in the core domain, amino acids 1-383 of RAG2, which is defined as a critical functional domain by the ClinGen SCID VCEP (PMID: 26996199); PM1_Supporting.\n", "contributionDate": { "date": "2024/5/14", "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": "CA380142798/MONDO:0000573/124/ci/CA380142798/MONDO:0000573/124.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA380142798/MONDO:0000573/124/0/1681/1683", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA380142798/MONDO:0000573/124/1/1682", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA380142798/MONDO:0000573/124/0/1681", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA380142798/MONDO:0000573/124/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA380142798/MONDO:0000573/124/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2024/5/14", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/007", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "007", "label": "PM3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA380142798/MONDO:0000573/124/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA380142798/MONDO:0000573/124/ci/CA380142798/MONDO:0000573/124.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "This variant has been detected in one individual with SCID, reported by Invitae in ClinVar. This individual is compound heterozygous for p.Gly95Arg, a likely pathogenic variant according to SCID VCEP specifications; Both parents were tested, phase is confirmed; 1 point. PM3_Moderate. (Internal lab contributor).", "contributionDate": { "date": "2024/5/14", "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": "CA380142798/MONDO:0000573/124/ci/CA380142798/MONDO:0000573/124.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA380142798/MONDO:0000573/124/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA380142798/MONDO:0000573/124/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA380142798/MONDO:0000573/124/0/1717", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA380142798/MONDO:0000573/124", "metadata": { "created": "2024-09-28T04:40:27.525Z", "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": "Sat, 28 Sep 2024 04:40:27 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26333-7", "id": "LN:LA26333-7", "label": "Uncertain Significance" }, "type": "VariantPathogenicityInterpretation", "uuid": "eeb69d61-f36f-44f5-bf81-a8d89de0be61", "variant": { "@id": "https://reg.genome.network/allele/CA380142798", "id": "CAR:CA380142798", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000536.4:c.501A>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000536.4(RAG2):c.501A>C (p.Arg167Ser)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-16T01:47:57.964Z" } }, "status": { "code": 200, "name": "OK" } }