{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/61f976ce-4a2b-4853-84a7-195a243610c2/doc/sepio/version/1.0.0", "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/CA294896504/MONDO:0009290/010/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896504/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": "2025/9/16", "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/CA294896504/MONDO:0009290/010/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA294896504/MONDO:0009290/010/ci/CA294896504/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 0.802 which is above the threshold of 0.7, evidence that correlates with impact to GAA function (PP3) .\n", "contributionDate": { "date": "2025/9/16", "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": "CA294896504/MONDO:0009290/010/ci/CA294896504/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA294896504/MONDO:0009290/010/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA294896504/MONDO:0009290/010/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA294896504/MONDO:0009290/010/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896504/MONDO:0009290/010/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896504/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": "2025/9/16", "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/CA294896504/MONDO:0009290/010/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA294896504/MONDO:0009290/010/ci/CA294896504/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)\n", "contributionDate": { "date": "2025/9/16", "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": "CA294896504/MONDO:0009290/010/ci/CA294896504/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA294896504/MONDO:0009290/010/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA294896504/MONDO:0009290/010/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA294896504/MONDO:0009290/010/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896504/MONDO:0009290/010/el/0/1825", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896504/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": "2025/9/16", "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/CA294896504/MONDO:0009290/010/el/0/1825/1827", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA294896504/MONDO:0009290/010/ci/CA294896504/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 HEK293 cells resulted in loss of GAA activity and western blot showing only the 110kDa band, suggesting abnormal GAA processing (unpublished data from the laboratory that published PMID: 36246652).", "contributionDate": { "date": "2025/9/16", "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": "CA294896504/MONDO:0009290/010/ci/CA294896504/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA294896504/MONDO:0009290/010/0/1825/1827", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA294896504/MONDO:0009290/010/1/1826", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA294896504/MONDO:0009290/010/0/1825", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896504/MONDO:0009290/010/el/0/1651", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896504/MONDO:0009290/010/ei/1/1652", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/9/16", "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/CA294896504/MONDO:0009290/010/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA294896504/MONDO:0009290/010/ci/CA294896504/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 reported in at least three individuals with features consistent with Pompe disease. Two are compound heterozygous for the variant and a variant in GAA classified as Pathogenic by the ClinGen LSD VCEP, phase known, including c.525delT (ClinVar # VCV000004033.83) (2 points) , c.-32-13T>G (ClinVar # VCV000004027.118) (PMID 28763149) (2 points). One infantile patient is documented only with the variant. No second variant reported (PMID:29044175)", "contributionDate": { "date": "2025/9/16", "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": "CA294896504/MONDO:0009290/010/ci/CA294896504/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA294896504/MONDO:0009290/010/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA294896504/MONDO:0009290/010/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA294896504/MONDO:0009290/010/0/1651", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896504/MONDO:0009290/010/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896504/MONDO:0009290/010/ei/1/1832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2025/9/16", "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/CA294896504/MONDO:0009290/010/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA294896504/MONDO:0009290/010/ci/CA294896504/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 three individuals with this variant had documented GAA deficiency- one within <10%of normal mean in leukocytes (PMID: 29044175) and two individuals with GAA activity below reference range in muscle (PMID:28763149), sufficient to meet the ClinGen LSD VCEP’s specifications for PP4_moderate", "contributionDate": { "date": "2025/9/16", "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": "CA294896504/MONDO:0009290/010/ci/CA294896504/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA294896504/MONDO:0009290/010/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA294896504/MONDO:0009290/010/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA294896504/MONDO:0009290/010/0/1831", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA294896504/MONDO:0009290/010", "metadata": { "created": "2025-09-16T20:04:19.810Z", "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, 16 Sep 2025 20:04:19 -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": "61f976ce-4a2b-4853-84a7-195a243610c2", "variant": { "@id": "https://reg.genome.network/allele/CA294896504", "id": "CAR:CA294896504", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000152.5:c.1880C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000152.5(GAA):c.1880C>T (p.Ser627Phe)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-26T21:57:03.231Z" } }, "status": { "code": 200, "name": "OK" } }