{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://erepo.genome.network/evrepo/api/summary/classification/20d691da-2b31-4fcc-bb92-9a9df416c0e6/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/643243138", "label": "ClinGen Epilepsy Sodium Channel Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SCN2A Version 2.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "2.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0100038", "id": "MONDO:0100038", "label": "complex neurodevelopmental disorder", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50105_EP171510966881719", "id": "CG-PCER-AGENT:CG_50105_EP171510966881719", "type": "Agent" }, "contributionDate": { "date": "2025/10/28", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA318202/MONDO:0100038/068/ci/CA318202/MONDO:0100038/068.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50105_EP171510966881719", "id": "CG-PCER-AGENT:CG_50105_EP171510966881719", "type": "Agent" }, "contributionDate": { "date": "2025/10/28", "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": "CA318202/MONDO:0100038/068/ci/CA318202/MONDO:0100038/068.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50105_EP171510966881719", "id": "CG-PCER-AGENT:CG_50105_EP171510966881719", "type": "Agent" }, "contributionDate": { "date": "2025/10/28", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA318202/MONDO:0100038/068/ci/CA318202/MONDO:0100038/068.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50105_EP171510966881719", "id": "CG-PCER-AGENT:CG_50105_EP171510966881719", "type": "Agent" }, "comments": "Other phenotypes not consistent w/neurodevelopmental disorder: 0 points (for supporting 1-1.5 points)\n\nPMID: 25131622. WES in 78 patients with various neurodevelopmental disabilities. Patient 72 has the SCN2A c.1526 A>G (K509R) variant. However, the inheritance is unknown. Phenotype: only serizures, MRI findings: normal. They described epileptic encephalopathy, early infantile, 11 (MIM# 613721) as the disease. \n\nThe phenotype evidence does not meet the complex Neurodevelopmental Disorder described by Helbig et al, 2018 (PMID: 30311377)\n\n", "contributionDate": { "date": "2025/10/28", "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": "CA318202/MONDO:0100038/068/ci/CA318202/MONDO:0100038/068.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/ei/1/1685", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50105_EP171510966881719", "id": "CG-PCER-AGENT:CG_50105_EP171510966881719", "type": "Agent" }, "contributionDate": { "date": "2025/10/28", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA318202/MONDO:0100038/068/ci/CA318202/MONDO:0100038/068.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50105_EP171510966881719", "id": "CG-PCER-AGENT:CG_50105_EP171510966881719", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.243 (REVEL threshold for BP4 supporting 0.183-0.290, PMID: 36413997), evidence that does not predict a damaging effect on SCN2A function (BP4).", "contributionDate": { "date": "2025/10/28", "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": "CA318202/MONDO:0100038/068/ci/CA318202/MONDO:0100038/068.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/el/0/1765", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/ei/1/1766", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50105_EP171510966881719", "id": "CG-PCER-AGENT:CG_50105_EP171510966881719", "type": "Agent" }, "contributionDate": { "date": "2025/10/28", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/el/0/1765/1767", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA318202/MONDO:0100038/068/ci/CA318202/MONDO:0100038/068.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50105_EP171510966881719", "id": "CG-PCER-AGENT:CG_50105_EP171510966881719", "type": "Agent" }, "comments": "NM_001040142.2(SCN2A):c.1527A>G (p.Lys509=) synonymous Likely benign\n\nSCN1A: no paralogous variants\nSCN3A: no P/LP variants\n NM_006922.4(SCN3A):c.1516AGA[1] (p.Arg507del) VUS\n NM_006922.4(SCN3A):c.1521A>C (p.Arg507Ser) LB\n NM_006922.4(SCN3A):c.1520G>A (p.Arg507Lys) LB\nSCN8A:\n NM_001330260.2(SCN8A):c.1497G>A (p.Lys499=) LB\t", "contributionDate": { "date": "2025/10/28", "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": "CA318202/MONDO:0100038/068/ci/CA318202/MONDO:0100038/068.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/0/1765/1767", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/1/1766", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/0/1765", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/ei/1/1616", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50105_EP171510966881719", "id": "CG-PCER-AGENT:CG_50105_EP171510966881719", "type": "Agent" }, "contributionDate": { "date": "2025/10/28", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA318202/MONDO:0100038/068/ci/CA318202/MONDO:0100038/068.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50105_EP171510966881719", "id": "CG-PCER-AGENT:CG_50105_EP171510966881719", "type": "Agent" }, "comments": "This variant does not reside within a region of SCN2A that is defined as a mutational hotspot or critical functional domain by the ClinGen Epilepsy Sodium Channel Expert Panel.", "contributionDate": { "date": "2025/10/28", "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": "CA318202/MONDO:0100038/068/ci/CA318202/MONDO:0100038/068.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50105_EP171510966881719", "id": "CG-PCER-AGENT:CG_50105_EP171510966881719", "type": "Agent" }, "contributionDate": { "date": "2025/10/28", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA318202/MONDO:0100038/068/ci/CA318202/MONDO:0100038/068.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50105_EP171510966881719", "id": "CG-PCER-AGENT:CG_50105_EP171510966881719", "type": "Agent" }, "comments": "NM_001040142.2(SCN2A):c.1527A>G (p.Lys509=) synonymous Likely benign\n\nSCN1A: no paralogous variants\nSCN3A: no P/LP variants\n NM_006922.4(SCN3A):c.1516AGA[1] (p.Arg507del) VUS\n NM_006922.4(SCN3A):c.1521A>C (p.Arg507Ser) LB\n NM_006922.4(SCN3A):c.1520G>A (p.Arg507Lys) LB\nSCN8A:\n NM_001330260.2(SCN8A):c.1497G>A (p.Lys499=) LB\t\n", "contributionDate": { "date": "2025/10/28", "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": "CA318202/MONDO:0100038/068/ci/CA318202/MONDO:0100038/068.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50105_EP171510966881719", "id": "CG-PCER-AGENT:CG_50105_EP171510966881719", "type": "Agent" }, "contributionDate": { "date": "2025/10/28", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA318202/MONDO:0100038/068/ci/CA318202/MONDO:0100038/068.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50105_EP171510966881719", "id": "CG-PCER-AGENT:CG_50105_EP171510966881719", "type": "Agent" }, "comments": "The filtering allele frequency (the lower threshold of the 95% CI of 21/1,613,966) of the c.1526A>G variant in SCN2A is 0.001144% (gnomAD v4.1.0) for Non-Finnish European chromosomes, which is higher than the ClinGen Epilepsy Sodium Channel Variant Curation Expert Panel threshold (>0.0002%) for BS1, and therefore meets this criterion BS1).", "contributionDate": { "date": "2025/10/28", "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": "CA318202/MONDO:0100038/068/ci/CA318202/MONDO:0100038/068.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50105_EP171510966881719", "id": "CG-PCER-AGENT:CG_50105_EP171510966881719", "type": "Agent" }, "contributionDate": { "date": "2025/10/28", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA318202/MONDO:0100038/068/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA318202/MONDO:0100038/068/ci/CA318202/MONDO:0100038/068.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50105_EP171510966881719", "id": "CG-PCER-AGENT:CG_50105_EP171510966881719", "type": "Agent" }, "comments": "Allele frequency is above 0.0002% in GnomAD v4.1.0 (0.001144%)", "contributionDate": { "date": "2025/10/28", "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": "CA318202/MONDO:0100038/068/ci/CA318202/MONDO:0100038/068.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068/0/1798", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA318202/MONDO:0100038/068", "metadata": { "created": "2025-10-28T14:49:04.818Z", "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, 28 Oct 2025 14:49:05 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26334-5", "id": "LN:LA26334-5", "label": "Likely Benign" }, "type": "VariantPathogenicityInterpretation", "uuid": "20d691da-2b31-4fcc-bb92-9a9df416c0e6", "variant": { "@id": "https://reg.genome.network/allele/CA318202", "id": "CAR:CA318202", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_001040142.2:c.1526A>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_001040142.2(SCN2A):c.1526A>G (p.Lys509Arg)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-06-15T08:29:00.718Z" } }, "status": { "code": 200, "name": "OK" } }