{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/2b5077ea-d72a-4564-a83c-2aea98c3b4a8/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 2.0", "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" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0009290", "id": "MONDO:0009290", "label": "glycogen storage disease II", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": 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"statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401363495/MONDO:0009290/010/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401363495/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": "2026/7/21", "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/CA401363495/MONDO:0009290/010/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA401363495/MONDO:0009290/010/ci/CA401363495/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" }, "contributionDate": { "date": "2026/7/21", "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": "CA401363495/MONDO:0009290/010/ci/CA401363495/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401363495/MONDO:0009290/010/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401363495/MONDO:0009290/010/ei/1/1685", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2026/7/21", "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/CA401363495/MONDO:0009290/010/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA401363495/MONDO:0009290/010/ci/CA401363495/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": "REVEL score = 0.476 which is lower than the LD VCEP threshold for BP4 (<0.5), and therefore meets this criterion.", "contributionDate": { "date": "2026/7/21", "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": "CA401363495/MONDO:0009290/010/ci/CA401363495/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401363495/MONDO:0009290/010/el/0/1765", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401363495/MONDO:0009290/010/ei/1/1766", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2026/7/21", "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/CA401363495/MONDO:0009290/010/el/0/1765/1767", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA401363495/MONDO:0009290/010/ci/CA401363495/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 p.Pro266Ser amino acid change has not been reported with another nucleotide change in ClinVar, HGMD Pro, LOVD or pompevariantdatabase.nl.", "contributionDate": { "date": "2026/7/21", "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": "CA401363495/MONDO:0009290/010/ci/CA401363495/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/0/1765/1767", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/1/1766", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/0/1765", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401363495/MONDO:0009290/010/el/0/1651", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401363495/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": "2026/7/21", "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/CA401363495/MONDO:0009290/010/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA401363495/MONDO:0009290/010/ci/CA401363495/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": "Seven patients with features consistent with Pompe disease are compound heterozygous for the variant and a variant in GAA classified as pathogenic or likely pathogenic by the ClinGen LD VCEP, phase unknown, including c.1309C>T (p.Arg437Cys) (PMID: 25526786; 0.5 points), c.1316T>A (p.Met439Lys) (PMID: 17092519, 31193175, 2 x 0.5 points), c.1935C>A (p.Asp645Glu) (PMID: 28394184) (ClinVar# SCV002032138.1) (0.5 points), c.546G>T (PMID: 29124014) (ClinVar# SCV002032139.1) (2 x 0.5 points), and c.1602_1605delinsAGG (p.Asn535GlyfsTer43) (PMID: 28394184) (0.25 points). Total 3.25 points (PM3_Strong). ", "contributionDate": { "date": "2026/7/21", "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": "CA401363495/MONDO:0009290/010/ci/CA401363495/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/0/1651", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401363495/MONDO:0009290/010/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401363495/MONDO:0009290/010/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2026/7/21", "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/CA401363495/MONDO:0009290/010/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA401363495/MONDO:0009290/010/ci/CA401363495/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": "A missense change (p.Pro266Leu, c.797C>T) at the same amino acid residue has been reported by ClinVar. Another missense change (p.Pro266Thr, c.796C>A) at the same amino acid residue is reported in literature. These variants have not been classified as pathogenic or likely pathogenic by the ClinGen LD VCEP. Therefore, PM5 is not met.", "contributionDate": { "date": "2026/7/21", "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": "CA401363495/MONDO:0009290/010/ci/CA401363495/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401363495/MONDO:0009290/010/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401363495/MONDO:0009290/010/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2026/7/21", "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/CA401363495/MONDO:0009290/010/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA401363495/MONDO:0009290/010/ci/CA401363495/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 resulted in 14-18% wild type GAA activity, in two different studies, when expressed in COS cells. (PMID: 18425781, 19862843). Western blot revealed presence of the active 76kDa GAA band, but at a much lower level than wild type (PMID: 19862843).", "contributionDate": { "date": "2026/7/21", "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": "CA401363495/MONDO:0009290/010/ci/CA401363495/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401363495/MONDO:0009290/010/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401363495/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": "2026/7/21", "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/CA401363495/MONDO:0009290/010/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA401363495/MONDO:0009290/010/ci/CA401363495/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 seven patients with this variant and features consistent with Pompe disease have been reported. This includes 2 patients with documented values showing deficient GAA activity (<10% normal or below reference range in leukocytes) (PMID: 17092519, 29124014) (PP4_Moderate).", "contributionDate": { "date": "2026/7/21", "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": "CA401363495/MONDO:0009290/010/ci/CA401363495/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010/0/1831", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA401363495/MONDO:0009290/010", "metadata": { "created": "2026-07-21T18:55:14.506Z", "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, 21 Jul 2026 18:55:14 -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": "2b5077ea-d72a-4564-a83c-2aea98c3b4a8", "variant": { "@id": "https://reg.genome.network/allele/CA401363495", "id": "CAR:CA401363495", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000152.5:c.796C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000152.5(GAA):c.796C>T (p.Pro266Ser)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-15T09:13:57.468Z" } }, "status": { "code": 200, "name": "OK" } }