{ "data": { "@context": "https://genboree.org/evrepo/api/context", "@id": "https://genboree.org/evrepo/api/summary/classification/fa6294cc-492f-4f73-aa81-7dcda9dd4721/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://genboree.org/evrepo/api/interpretation/CA401361913/MONDO:0009290/010/el/0/1594", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA401361913/MONDO:0009290/010/ei/1/1595", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50009_EP157152691811958", "id": "CG-PCER-AGENT:CG_50009_EP157152691811958", "type": "Agent" }, "contributionDate": { "date": "2025/7/2", "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://genboree.org/evrepo/api/interpretation/CA401361913/MONDO:0009290/010/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA401361913/MONDO:0009290/010/ci/CA401361913/MONDO:0009290/010.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50009_EP157152691811958", "id": "CG-PCER-AGENT:CG_50009_EP157152691811958", "type": "Agent" }, "comments": "The NM_000152.5:c.546+1G>T variant in GAA occurs within the canonical splice donor site of intron 2. Two studies involving minigene analysis have showed that the variant disrupts normal splicing, resulting in skipping of exon 2 (PMID: 31301153, 39905333). Exon 2 contains the start methionine and signal sequence for GAA (amino acids 1-27; https://www.uniprot.org/uniprot/P10253). Deletion of exon 2 causes complete loss of enzyme activity when expressed in heterologous cells (Huie et al, 1994, PMID 7881425; Boerkoel et al, 1995, PMID 7717400) (PVS1). ", "contributionDate": { "date": "2025/7/2", "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": "CA401361913/MONDO:0009290/010/ci/CA401361913/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA401361913/MONDO:0009290/010/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401361913/MONDO:0009290/010/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401361913/MONDO:0009290/010/0/1594", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA401361913/MONDO:0009290/010/el/0/1831", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA401361913/MONDO:0009290/010/ei/1/1832", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50009_EP157152691811958", "id": "CG-PCER-AGENT:CG_50009_EP157152691811958", "type": "Agent" }, "contributionDate": { "date": "2025/7/2", "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://genboree.org/evrepo/api/interpretation/CA401361913/MONDO:0009290/010/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA401361913/MONDO:0009290/010/ci/CA401361913/MONDO:0009290/010.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50009_EP157152691811958", "id": "CG-PCER-AGENT:CG_50009_EP157152691811958", "type": "Agent" }, "comments": "At least 5 probands with symptoms consistent with late-onset Pompe disease have been reported with this variant (PMID: 18285536, 25396301, 25712382, 28838325), one with documented GAA deficiency with <10% of normal mean control level of GAA activity in a muscle sample (PP4_Moderate).", "contributionDate": { "date": "2025/7/2", "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": "CA401361913/MONDO:0009290/010/ci/CA401361913/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA401361913/MONDO:0009290/010/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401361913/MONDO:0009290/010/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401361913/MONDO:0009290/010/0/1831", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA401361913/MONDO:0009290/010/el/0/1717", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA401361913/MONDO:0009290/010/ei/1/1718", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50009_EP157152691811958", "id": "CG-PCER-AGENT:CG_50009_EP157152691811958", "type": "Agent" }, "contributionDate": { "date": "2025/7/2", "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://genboree.org/evrepo/api/interpretation/CA401361913/MONDO:0009290/010/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA401361913/MONDO:0009290/010/ci/CA401361913/MONDO:0009290/010.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50009_EP157152691811958", "id": "CG-PCER-AGENT:CG_50009_EP157152691811958", "type": "Agent" }, "comments": "This variant has been detected in at least 5 individuals with Pompe disease. Of those individuals, 4 were compound heterozygous for this variant and another variant in GAA that has been classified as pathogenic by the ClinGen LD VCEP, c.-32-13T>G, phase unconfirmed (PMID: 18285536, 25396301, 25712382, 28838325; max 2 x 0.5 points) (PM3).", "contributionDate": { "date": "2025/7/2", "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": "CA401361913/MONDO:0009290/010/ci/CA401361913/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA401361913/MONDO:0009290/010/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401361913/MONDO:0009290/010/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401361913/MONDO:0009290/010/0/1717", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA401361913/MONDO:0009290/010/el/0/1636", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA401361913/MONDO:0009290/010/ei/1/1637", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50009_EP157152691811958", "id": "CG-PCER-AGENT:CG_50009_EP157152691811958", "type": "Agent" }, "contributionDate": { "date": "2025/7/2", "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://genboree.org/evrepo/api/interpretation/CA401361913/MONDO:0009290/010/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA401361913/MONDO:0009290/010/ci/CA401361913/MONDO:0009290/010.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50009_EP157152691811958", "id": "CG-PCER-AGENT:CG_50009_EP157152691811958", "type": "Agent" }, "comments": "This variant is absent in gnomAD v4.1.0. (PM2_Supporting).", "contributionDate": { "date": "2025/7/2", "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": "CA401361913/MONDO:0009290/010/ci/CA401361913/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA401361913/MONDO:0009290/010/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401361913/MONDO:0009290/010/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401361913/MONDO:0009290/010/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401361913/MONDO:0009290/010", "metadata": { "created": "2025-07-02T20:04:08.393Z", "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": "Wed, 02 Jul 2025 20:04:08 -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": "fa6294cc-492f-4f73-aa81-7dcda9dd4721", "variant": { "@id": "https://reg.genome.network/allele/CA401361913", "id": "CAR:CA401361913", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000152.5:c.546+1G>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000152.5(GAA):c.546+1G>T" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://genboree.org/evrepo/api/summarysrvc", "when": "2026-06-01T17:39:36.230Z" } }, "status": { "code": 200, "name": "OK" } }