{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/10e16111-a4ca-4f6d-9251-2d3539039820/doc/sepio/version/1.0.0", "assertionMethod": { "type": "VariantPathogenicityInterpretationGuideline" }, "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/CA294896907/MONDO:0009290/010/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896907/MONDO:0009290/010/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2020/5/28", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0011", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0011", "label": "PM2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896907/MONDO:0009290/010/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA294896907/MONDO:0009290/010/ci/CA294896907/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 highest population minor allele frequency in gnomAD v2.1.1 is 0.0000489 in the Finnish population. This variant is not present in any other population in gnomAD v2.1.1, meeting PM2.", "contributionDate": { "date": "2020/5/28", "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": "CA294896907/MONDO:0009290/010/ci/CA294896907/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896907/MONDO:0009290/010/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896907/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": "2020/5/28", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0062", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0062", "label": "PP3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896907/MONDO:0009290/010/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA294896907/MONDO:0009290/010/ci/CA294896907/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": "Multiple lines of computational evidence predict that this variant is deleterious. The PROVEAN score is -12.376 (meeting the threshold of -2.5 for deleterious), and Mutation Taster predicts that this variant is \"disease causing”.", "contributionDate": { "date": "2020/5/28", "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": "CA294896907/MONDO:0009290/010/ci/CA294896907/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896907/MONDO:0009290/010/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896907/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": "2020/5/28", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0063", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0063", "label": "PP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896907/MONDO:0009290/010/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA294896907/MONDO:0009290/010/ci/EV000000988", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "In a study of Indian patients with suspected lysosomal storage disorders, 3 patients were identified with variants in GAA, at least one of whom had this variant and p.Asp489Asn (from the data, it is not clear if one or two patients have this genotype). The range of GAA activity, measured in skin fibroblasts, for these patients is 2.4-5.6 nmol/h/mg. However, because the reference range not provided in the paper, this data cannot be included.", "contributionDate": { "date": "2020/5/28", "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": "CA294896907/MONDO:0009290/010/ci/EV000000988", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/22791670", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896907/MONDO:0009290/010/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896907/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": "2020/5/28", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/007", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "007", "label": "PM3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896907/MONDO:0009290/010/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA294896907/MONDO:0009290/010/ci/EV000000989", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "The paper describes an Indian family with a previously child affected by infantile onset Pompe disease who passed away. No genetic testing was performed on the child and no results for residual GAA activity are provided. Both parents are heterozygous for a variant in GAA; one for p.Gly655del and one for p.Asp489Asn. It is unlcear whether this family is also reported in PMID 22791670.", "contributionDate": { "date": "2020/5/28", "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": "CA294896907/MONDO:0009290/010/ci/EV000000989", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/22711147", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA294896907/MONDO:0009290/010/ci/EV000000988", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "A patient is described who is compound heterozygous for p.Gln355del and p.Asp489Asn (from the data, it is not clear if one or two patients have this genotype). The range of GAA activity, measured in skin fibroblasts, for these patients is 2.4-5.6 nmol/h/mg; reference range not provided. p.Asp489Asn has multiple submitters in ClinVar and is classified as pathogenic/likely pathogenic.", "contributionDate": { "date": "2020/5/28", "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": "CA294896907/MONDO:0009290/010/ci/EV000000988", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/22791670", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896907/MONDO:0009290/010/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896907/MONDO:0009290/010/ei/1/1829", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2020/5/28", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0052", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0052", "label": "PS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896907/MONDO:0009290/010/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA294896907/MONDO:0009290/010/ci/EV000000987", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "comments": "Transient expression of this variant in COS-7 cells resulted in low GAA activity (2% of wild type activity in cells, and 0% in the medium). Western blot revealed abnormal GAA processing with reduced levels of the active 76 kDa species in cells and medium. The variant was classified as Class B (“potentially less severe”).", "contributionDate": { "date": "2020/5/28", "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": "CA294896907/MONDO:0009290/010/ci/EV000000987", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/18425781", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896907/MONDO:0009290/010/el/0/1714", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896907/MONDO:0009290/010/ei/1/1715", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718", "id": "CG-PCER-AGENT:CG_50009_EP157972030954718", "type": "Agent" }, "contributionDate": { "date": "2020/5/28", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0059", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0059", "label": "PM4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA294896907/MONDO:0009290/010/el/0/1714/1716", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA294896907/MONDO:0009290/010/ci/CA294896907/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 results in an inframe single amino acid deletion (p.Glu655del) in GAA, meeting the ClinGen LSD VCEP criteria for PM4_Supporting.", "contributionDate": { "date": "2020/5/28", "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": "CA294896907/MONDO:0009290/010/ci/CA294896907/MONDO:0009290/010.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/0/1714/1716", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/1/1715", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010/0/1714", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA294896907/MONDO:0009290/010", "metadata": { "created": "2024-09-27T20:52:23.706Z", "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": "Fri, 27 Sep 2024 20:52:23 -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": "10e16111-a4ca-4f6d-9251-2d3539039820", "variant": { "@id": "https://reg.genome.network/allele/CA294896907", "id": "CAR:CA294896907", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000152.5:c.1962_1964del" } ], "preferred": true } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-28T23:48:06.674Z" } }, "status": { "code": 200, "name": "OK" } }