{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/213e71e7-cd11-4a68-95a4-1ffff19be08c/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1811993349", "label": "ClinGen Limb Girdle Muscular Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SGCB Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0015152", "id": "MONDO:0015152", "label": "autosomal recessive limb-girdle muscular dystrophy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2918420/MONDO:0015152/184/el/0/1651", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2918420/MONDO:0015152/184/ei/1/1652", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2025/1/8", "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/CA2918420/MONDO:0015152/184/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2918420/MONDO:0015152/184/ci/CA2918420/MONDO:0015152/184.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "This variant has been detected in at least 10 individuals with limb girdle muscular dystrophy, including in a homozygous state in four (1.0 pt) and confirmed in trans with a likely pathogenic or pathogenic variant in two (c.699_702del, 1.0 pt; c.85A>T p.(Arg29Ter), 1.0 pt); (PMID: 25862795, 36077211, 10662809; PM3_Strong).\n\nARC: \nSemplicini et al. report 3 homozygous probands (2 consang, 1 not; (1.0 pt) and 3 compound hets: c.699_702del (1.0 pt), c.552T>G p.(Tyr184Ter) (uncurated), c.85A>T p.(Arg29Ter) (1.0 pt).\n\nc.243+3_243+6del and c.243+1548T>C uncurated\n\nOverall:\n4 hom: 2 consang (0.25 x2), 2 non-consang (0.5 x2) = 1 pt\n6 comp het, with 2 confirmed LP/P = 2 pt ", "contributionDate": { "date": "2025/1/8", "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": "CA2918420/MONDO:0015152/184/ci/CA2918420/MONDO:0015152/184.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2918420/MONDO:0015152/184/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2918420/MONDO:0015152/184/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2918420/MONDO:0015152/184/0/1651", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2918420/MONDO:0015152/184/el/0/1630", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2918420/MONDO:0015152/184/ei/1/1631", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2025/1/8", "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/CA2918420/MONDO:0015152/184/el/0/1630/1632", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2918420/MONDO:0015152/184/ci/CA2918420/MONDO:0015152/184.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "This variant has been reported to segregate with autosomal recessive LGMD in two affected family members from two Italian families (PMID: 25862795).\n\nARC note: Semplicini et al. (2015) supplementary table shows 2 pairs of homozygous siblings (3 & 4, 9 & 16.", "contributionDate": { "date": "2025/1/8", "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": "CA2918420/MONDO:0015152/184/ci/CA2918420/MONDO:0015152/184.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2918420/MONDO:0015152/184/0/1630/1632", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2918420/MONDO:0015152/184/1/1631", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2918420/MONDO:0015152/184/0/1630", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2918420/MONDO:0015152/184/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2918420/MONDO:0015152/184/ei/1/1595", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2025/1/8", "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/CA2918420/MONDO:0015152/184/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2918420/MONDO:0015152/184/ci/CA2918420/MONDO:0015152/184.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "The NM_000232.5: c.377_384dup p.(Gly129GlnfsTer2) variant in SGCB is a duplication of nucleotides 377-384 predicted to cause a frameshift and premature stop codon in biologically relevant exon 3/6, leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (PVS1).", "contributionDate": { "date": "2025/1/8", "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": "CA2918420/MONDO:0015152/184/ci/CA2918420/MONDO:0015152/184.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2918420/MONDO:0015152/184/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2918420/MONDO:0015152/184/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2918420/MONDO:0015152/184/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2918420/MONDO:0015152/184/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2918420/MONDO:0015152/184/ei/1/1832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2025/1/8", "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/CA2918420/MONDO:0015152/184/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2918420/MONDO:0015152/184/ci/CA2918420/MONDO:0015152/184.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "At least one patient with this variant showed a progressive LGMD phenotype and significantly reduced expression of β-sarcoglycan in skeletal muscle, which is highly specific for SGCB-related LGMD (PP4_Moderate (capped with PP1); PMID: 36077211).\n\nARC: cannot confirm screening of all SGC genes in Semplicini patients. Magri et al. patient had a panel test and <30% normal expression of all 4 SGC genes. ", "contributionDate": { "date": "2025/1/8", "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": "CA2918420/MONDO:0015152/184/ci/CA2918420/MONDO:0015152/184.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2918420/MONDO:0015152/184/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2918420/MONDO:0015152/184/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2918420/MONDO:0015152/184/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2918420/MONDO:0015152/184/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2918420/MONDO:0015152/184/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2025/1/8", "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/CA2918420/MONDO:0015152/184/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2918420/MONDO:0015152/184/ci/CA2918420/MONDO:0015152/184.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "The minor allele frequency of this variant is 0.000008791 in the European (non-Finnish) population in gnomAD v2.1.1 (1/113750 exome chromosomes), which is lower than the LGMD VCEP threshold (<0.00009) for PM2_Supporting, meeting this criterion (PM2_Supporting).", "contributionDate": { "date": "2025/1/8", "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": "CA2918420/MONDO:0015152/184/ci/CA2918420/MONDO:0015152/184.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2918420/MONDO:0015152/184/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2918420/MONDO:0015152/184/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2918420/MONDO:0015152/184/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2918420/MONDO:0015152/184", "metadata": { "created": "2025-01-08T15:19:42.713Z", "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, 08 Jan 2025 15:19:42 -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": "213e71e7-cd11-4a68-95a4-1ffff19be08c", "variant": { "@id": "https://reg.genome.network/allele/CA2918420", "id": "CAR:CA2918420", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000232.5:c.377_384dup" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000232.5(SGCB):c.377_384dup (p.Gly129delinsGlnTer)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-02T16:00:25.094Z" } }, "status": { "code": 200, "name": "OK" } }