{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://erepo.genome.network/evrepo/api/summary/classification/c6dcc9ff-882d-4aaa-972c-0d114fdabf56/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1610842289", "label": "ClinGen Antibody Deficiencies Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PIK3CD Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0014222", "id": "MONDO:0014222", "label": "immunodeficiency 14", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA577276/MONDO:0014222/141/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA577276/MONDO:0014222/141/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "contributionDate": { "date": "2025/12/23", "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/CA577276/MONDO:0014222/141/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA577276/MONDO:0014222/141/ci/CA577276/MONDO:0014222/141.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.349, which is below the ClinGen Antibody Deficiencies VCEP threshold of >0.644 and does not predict a damaging effect on PIK3CD function. The computational predictor CADD gives a PHRED score of 29.0, which is above the ClinGen Antibody Deficiencies VCEP threshold of >25.3 and predicts a deleterious effect on PIK3CD function. Because the two predictors do not agree on a damaging effect, the PP3 code is not met.", "contributionDate": { "date": "2025/12/23", "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": "CA577276/MONDO:0014222/141/ci/CA577276/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA577276/MONDO:0014222/141/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA577276/MONDO:0014222/141/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "contributionDate": { "date": "2025/12/23", "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/CA577276/MONDO:0014222/141/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA577276/MONDO:0014222/141/ci/CA577276/MONDO:0014222/141.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "comments": "Clinical Features:\nRecurrent fever (present) = 2 points (recurrent infection?)\n Neurodevelopmental abnormality (present) = 2 points (developmental delay?)\nDiarrhea (present) = 1 point (failure to thrive?)\n 5 PS4 points?", "contributionDate": { "date": "2025/12/23", "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": "CA577276/MONDO:0014222/141/ci/CA577276/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA577276/MONDO:0014222/141/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA577276/MONDO:0014222/141/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "contributionDate": { "date": "2025/12/23", "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/CA577276/MONDO:0014222/141/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA577276/MONDO:0014222/141/ci/CA577276/MONDO:0014222/141.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "comments": "The NM_005026.5(PIK3CD):c.1643G>A (p.Arg548Gln) is classified as VUS by the Antibody VCEP rules. ", "contributionDate": { "date": "2025/12/23", "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": "CA577276/MONDO:0014222/141/ci/CA577276/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA577276/MONDO:0014222/141/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA577276/MONDO:0014222/141/ei/1/1685", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "contributionDate": { "date": "2025/12/23", "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/CA577276/MONDO:0014222/141/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA577276/MONDO:0014222/141/ci/CA577276/MONDO:0014222/141.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "contributionDate": { "date": "2025/12/23", "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": "CA577276/MONDO:0014222/141/ci/CA577276/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA577276/MONDO:0014222/141/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA577276/MONDO:0014222/141/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "contributionDate": { "date": "2025/12/23", "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/CA577276/MONDO:0014222/141/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA577276/MONDO:0014222/141/ci/CA577276/MONDO:0014222/141.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "comments": "This variant has been reported in 1 affected proband with a phenotype including recurrent fever, neurodevelopmental abnormalities (0.5 pts), and diarrhea (1 pt), which are not sufficient to meet the phenotype requirements for inclusion of the proband in PS4_Supporting (1.5 total points, ClinVar Accession #: SCV002524004.1).", "contributionDate": { "date": "2025/12/23", "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": "CA577276/MONDO:0014222/141/ci/CA577276/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA577276/MONDO:0014222/141/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA577276/MONDO:0014222/141/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "contributionDate": { "date": "2025/12/23", "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/CA577276/MONDO:0014222/141/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA577276/MONDO:0014222/141/ci/CA577276/MONDO:0014222/141.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "comments": "This variant is present in gnomAD v.4.1.0 at a GrpMax allele frequency of 0.0001338, with 3 alleles / 6,074 total alleles in the Middle Eastern population, which is lower than the BS1 threshold of >0.000316, so no population code can be applied.", "contributionDate": { "date": "2025/12/23", "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": "CA577276/MONDO:0014222/141/ci/CA577276/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA577276/MONDO:0014222/141/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA577276/MONDO:0014222/141/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "contributionDate": { "date": "2025/12/23", "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/CA577276/MONDO:0014222/141/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA577276/MONDO:0014222/141/ci/CA577276/MONDO:0014222/141.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "comments": "This variant is present in gnomAD v4.1.0 at a total combined allele frequency of 0.00003730, with 60 alleles / 1,608,744 total alleles across all populations of gnomAD, which is higher than the ClinGen Antibody Deficiencies VCEP PM2_Supporting threshold of <0.00000132.", "contributionDate": { "date": "2025/12/23", "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": "CA577276/MONDO:0014222/141/ci/CA577276/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141/0/1798", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA577276/MONDO:0014222/141", "metadata": { "created": "2025-12-23T20:47:03.948Z", "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, 23 Dec 2025 20:47:03 -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": "c6dcc9ff-882d-4aaa-972c-0d114fdabf56", "variant": { "@id": "https://reg.genome.network/allele/CA577276", "id": "CAR:CA577276", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_005026.5:c.1642C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_005026.5(PIK3CD):c.1642C>T (p.Arg548Trp)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-05-24T16:41:12.462Z" } }, "status": { "code": 200, "name": "OK" } }