{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/32998b1b-724b-48dd-8e77-ff28373954c1/doc/sepio/version/1.2.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/135637582", "label": "ClinGen Lysosomal Storage Disorders Variant Curation Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2", "type": "VariantPathogenicityInterpretationGuideline", "url": "https://clinicalgenome.org/docs/clingen-lysosomal-storage-disorders-expert-panel-specifications-to-the-acmg-amp-variant-interpretation-guidelines-version-2/", "version": "2.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0009290", "id": "MONDO:0009290", "label": "glycogen storage disease II", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401366794/MONDO:0009290/010/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401366794/MONDO:0009290/010/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/10/28", "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/CA401366794/MONDO:0009290/010/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA401366794/MONDO:0009290/010/ci/CA401366794/MONDO:0009290/010.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.948 which is above the threshold of 0.7, evidence that correlates with impact to GAA function (PP3).", "contributionDate": { "date": "2025/10/28", "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": "CA401366794/MONDO:0009290/010/ci/CA401366794/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401366794/MONDO:0009290/010/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401366794/MONDO:0009290/010/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/10/28", "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/CA401366794/MONDO:0009290/010/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA401366794/MONDO:0009290/010/ci/CA401366794/MONDO:0009290/010.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "At least 1 patient(s) with this variant was reported to be on enzyme replacement therapy for Pompe disease (PMID: 31392188) (PP4).\n", "contributionDate": { "date": "2025/10/28", "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": "CA401366794/MONDO:0009290/010/ci/CA401366794/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401366794/MONDO:0009290/010/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401366794/MONDO:0009290/010/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/10/28", "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/CA401366794/MONDO:0009290/010/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA401366794/MONDO:0009290/010/ci/CA401366794/MONDO:0009290/010.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "This variant is absent in gnomAD v4.1.0 (PM2_Supporting).", "contributionDate": { "date": "2025/10/28", "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": "CA401366794/MONDO:0009290/010/ci/CA401366794/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401366794/MONDO:0009290/010/el/0/1825", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401366794/MONDO:0009290/010/ei/1/1826", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/10/28", "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/CA401366794/MONDO:0009290/010/el/0/1825/1827", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA401366794/MONDO:0009290/010/ci/CA401366794/MONDO:0009290/010.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "Expression of the variant in COS7 cells resulted in 0% wild type GAA activity and evidence of abnormal GAA synthesis and processing leading the variant to be described as Class B (“potentially less severe”), indicating that this variant may impact protein function (PMID 22644586) (PS3_Moderate).", "contributionDate": { "date": "2025/10/28", "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": "CA401366794/MONDO:0009290/010/ci/CA401366794/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/0/1825/1827", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/1/1826", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/0/1825", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401366794/MONDO:0009290/010/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401366794/MONDO:0009290/010/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/10/28", "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/CA401366794/MONDO:0009290/010/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA401366794/MONDO:0009290/010/ci/CA401366794/MONDO:0009290/010.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "This variant has been detected two apparently unrelated probands and one sibling with late onset Pompe disease who were compound heterozygous for the variant and another variant in GAA that has been classified as pathogenic for Pompe disease by the ClinGen LD VCEP, c.-32-13T>G; the phase is unknown (PMID: 24383498, 29122469, 31392188, 31710733, 38313679); 2 x 0.5pt) (PM3). \n", "contributionDate": { "date": "2025/10/28", "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": "CA401366794/MONDO:0009290/010/ci/CA401366794/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401366794/MONDO:0009290/010/el/0/1774", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401366794/MONDO:0009290/010/ei/1/1775", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/10/28", "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/CA401366794/MONDO:0009290/010/el/0/1774/1776", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA401366794/MONDO:0009290/010/ci/CA401366794/MONDO:0009290/010.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "Two other missense variants at the same amino acids have been reported in patients with Pompe disease; c.1445C>T (p.Pro482Leu) (ClinVar Variation ID: 982297) has been classified as likely pathogenic by the ClinGen LD VCEP, c.1444C>T (p.Pro482Ser) has not yet been classified by the VCEP (PM5_Supporting). ", "contributionDate": { "date": "2025/10/28", "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": "CA401366794/MONDO:0009290/010/ci/CA401366794/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/0/1774/1776", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/1/1775", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010/0/1774", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401366794/MONDO:0009290/010", "metadata": { "created": "2025-10-28T21:10:36.678Z", "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, 28 Oct 2025 21:10:36 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.2.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "32998b1b-724b-48dd-8e77-ff28373954c1", "variant": { "@id": "https://reg.genome.network/allele/CA401366794", "id": "CAR:CA401366794", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000152.5:c.1445C>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000152.5(GAA):c.1445C>G (p.Pro482Arg)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T18:15:39.676Z" } }, "status": { "code": 200, "name": "OK" } }