{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://erepo.genome.network/evrepo/api/summary/classification/34e3113f-ad65-4155-abd8-4675d7d78cb0/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/CA338304786/MONDO:0014222/141/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338304786/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/CA338304786/MONDO:0014222/141/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA338304786/MONDO:0014222/141/ci/CA338304786/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 0.231, which is below the ClinGen Antibody Deficiencies VCEP threshold of <0.290 and predicts a non-damaging effect on PIK3CD function. The computational predictor CADD gives a PHRED score of 16.99, which is below the ClinGen Antibody Deficiencies VCEP threshold of <22.7 and predicts a non-deleterious effect on PIK3CD function. The two predictors agree on a non-damaging effect (BP4).", "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": "CA338304786/MONDO:0014222/141/ci/CA338304786/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA338304786/MONDO:0014222/141/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338304786/MONDO:0014222/141/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA338304786/MONDO:0014222/141/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338304786/MONDO:0014222/141/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338304786/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/CA338304786/MONDO:0014222/141/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA338304786/MONDO:0014222/141/ci/CA338304786/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 variant has been observed in at least one individual subjected to genetic testing, however it is not clear whether the individual was affected with a relevant clinical condition (SCV003968830.2).", "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": "CA338304786/MONDO:0014222/141/ci/CA338304786/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA338304786/MONDO:0014222/141/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338304786/MONDO:0014222/141/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA338304786/MONDO:0014222/141/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338304786/MONDO:0014222/141/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338304786/MONDO:0014222/141/ei/1/1637", "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/CA338304786/MONDO:0014222/141/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA338304786/MONDO:0014222/141/ci/CA338304786/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 absent from gnomAD v4.1.0 (PM2_Supporting).", "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": "CA338304786/MONDO:0014222/141/ci/CA338304786/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA338304786/MONDO:0014222/141/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338304786/MONDO:0014222/141/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA338304786/MONDO:0014222/141/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338304786/MONDO:0014222/141/el/0/1588", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338304786/MONDO:0014222/141/ei/1/1589", "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/CA338304786/MONDO:0014222/141/el/0/1588/1590", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA338304786/MONDO:0014222/141/ci/EV000001940", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "comments": "A base editing screen in primary T cells introducing another variant at the same codon, p.Leu668Pro, showed a log2 enrichment score of 0.82059 in the high-phospho-AKT / high-phospho-S6 fraction of cells relative to the low-phospho-AKT / low-phospho-S6 fraction of cells, with a two-sided p-value of 0.12839, indicating no significant disruption of the PI3K pathway (PMID: 40543502). Because this is a different amino acid change, BS3_Supporting was not evaluated.", "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": "CA338304786/MONDO:0014222/141/ci/EV000001940", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/40543502", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA338304786/MONDO:0014222/141/0/1588/1590", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338304786/MONDO:0014222/141/1/1589", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA338304786/MONDO:0014222/141/0/1588", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338304786/MONDO:0014222/141", "metadata": { "created": "2025-12-23T20:29:27.062Z", "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 20:29:26 -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": "34e3113f-ad65-4155-abd8-4675d7d78cb0", "variant": { "@id": "https://reg.genome.network/allele/CA338304786", "id": "CAR:CA338304786", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_005026.5:c.2002C>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_005026.5(PIK3CD):c.2002C>A (p.Leu668Met)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-05-24T16:41:05.248Z" } }, "status": { "code": 200, "name": "OK" } }