{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/41ba4c10-055f-4122-a444-abd8a5e0815e/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1528072643", "label": "ClinGen Platelet Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GP9 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0009276", "id": "MONDO:0009276", "label": "Bernard-Soulier syndrome", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447789/MONDO:0009276/083/el/0/1651", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447789/MONDO:0009276/083/ei/1/1652", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/2/14", "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/CA354447789/MONDO:0009276/083/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA354447789/MONDO:0009276/083/ci/CA354447789/MONDO:0009276/083.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "This variant has been detected in at least 7 probands with Bernard-Soulier syndrome. Of those individuals, 2 were compound heterozygous for this variant and a pathogenic or likely pathogenic variant and both of those were confirmed in trans by family testing or other methods (c. 212T>C [p.Phe71Ser], c.182A>G [p.Asn61Ser]. The proband compound heterozygous for the p.Phe71Ser variant was already scored in the p.Phe71Ser curation, so it was not awarded points. 1.0 PM3 points, PMIDs: 24934643, 28765788). The other 5 probands were homozygous for the variant, with at least 2 of these confirmed in trans (1.0 PM3 points, PMIDs: 24934643, 16916536, 8972003). Total points: 2.0 (PM3_Strong).", "contributionDate": { "date": "2025/2/14", "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": "CA354447789/MONDO:0009276/083/ci/CA354447789/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/0/1651", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447789/MONDO:0009276/083/el/0/1690", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447789/MONDO:0009276/083/ei/1/1691", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/2/14", "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/CA354447789/MONDO:0009276/083/el/0/1690/1692", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA354447789/MONDO:0009276/083/ci/CA354447789/MONDO:0009276/083.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.926, which is above the ClinGen PD VCEP threshold of >0.773 and predicts a damaging effect on function (PP3_Moderate).", "contributionDate": { "date": "2025/2/14", "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": "CA354447789/MONDO:0009276/083/ci/CA354447789/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/0/1690/1692", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/1/1691", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/0/1690", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447789/MONDO:0009276/083/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447789/MONDO:0009276/083/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/2/14", "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/CA354447789/MONDO:0009276/083/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA354447789/MONDO:0009276/083/ci/CA354447789/MONDO:0009276/083.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "The Grpmax filtering allele frequency in gnomaDv4.0.0 is 0.00007155 (based on 6/36062 alleles) in the East Asian population, which is above the ClinGen PD VCEP PM2_supporting threshold (<0.0000329) but below the BS1 threshold (>0.0007).", "contributionDate": { "date": "2025/2/14", "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": "CA354447789/MONDO:0009276/083/ci/CA354447789/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447789/MONDO:0009276/083/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447789/MONDO:0009276/083/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/2/14", "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/CA354447789/MONDO:0009276/083/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA354447789/MONDO:0009276/083/ci/CA354447789/MONDO:0009276/083.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "Surface expression of GP1a and GP9 measured by flow cytometry in CHO DUK- cells transiently co-transfected with the c.266G>A variant in GP9 and wild type GP1a and GP1b showed absent expression (<25%) WT levels, indicating that this variant impacts protein function (PMID:8972003)(PS3_supporting).\n", "contributionDate": { "date": "2025/2/14", "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": "CA354447789/MONDO:0009276/083/ci/CA354447789/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447789/MONDO:0009276/083/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447789/MONDO:0009276/083/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/2/14", "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/CA354447789/MONDO:0009276/083/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA354447789/MONDO:0009276/083/ci/CA354447789/MONDO:0009276/083.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "The Grpmax filtering allele frequency in gnomaDv4.1 is 0.00005788 (based on 6/44880 alleles) in the East Asian population, which is above the ClinGen PD VCEP PM2_supporting threshold (<0.0000329) but below the BS1 threshold (>0.0007).", "contributionDate": { "date": "2025/2/14", "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": "CA354447789/MONDO:0009276/083/ci/CA354447789/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447789/MONDO:0009276/083/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447789/MONDO:0009276/083/ei/1/1832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/2/14", "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/CA354447789/MONDO:0009276/083/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA354447789/MONDO:0009276/083/ci/CA354447789/MONDO:0009276/083.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": " At least one patient (Case 1 in PMID:8972003) with this variant had less than 10% expression of GPIba measured by Western blot, which is highly specific for Bernard-Soulier syndrome, in addition to macrothrombocytopenia. This proband received full gene sequencing and del/dup analysis of all BSS genes, with the only abnormality being \"two or three tandem repeats of a 13-amino acid sequence in the mucin-like macroglycopeptide region in GPIBa.\" In one study of this region in 206 individuals, it was reported that the triple repeat variant had an allele frequency of 7% in the Japanese population and 1% in the caucasian population. The double repeat of the 13 amino acid sequence was found at 1% in the Japanese population and 11% in individuals of caucasian ancestry (PMID: 1577776). \n", "contributionDate": { "date": "2025/2/14", "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": "CA354447789/MONDO:0009276/083/ci/CA354447789/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447789/MONDO:0009276/083/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA354447789/MONDO:0009276/083/ei/1/1679", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "contributionDate": { "date": "2025/2/14", "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/CA354447789/MONDO:0009276/083/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA354447789/MONDO:0009276/083/ci/CA354447789/MONDO:0009276/083.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50040_EP161161244771392", "id": "CG-PCER-AGENT:CG_50040_EP161161244771392", "type": "Agent" }, "comments": "The variant has been reported to segregate with Bernard-Soulier syndrome in the proband (meeting PP4) plus one affected family member (sister in family 1), both with the homozygous genotype with the c.266G>A variant. In the same paper, the variant was reported to segregate with BSS in the proband and one affected member of family 2. Both family members were homozygous. (PP1; PMID:8972003). \n", "contributionDate": { "date": "2025/2/14", "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": "CA354447789/MONDO:0009276/083/ci/CA354447789/MONDO:0009276/083.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083/0/1678", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA354447789/MONDO:0009276/083", "metadata": { "created": "2025-02-14T21:38:01.164Z", "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, 14 Feb 2025 21:38:01 -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": "41ba4c10-055f-4122-a444-abd8a5e0815e", "variant": { "@id": "https://reg.genome.network/allele/CA354447789", "id": "CAR:CA354447789", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000174.5:c.266G>A" } ], "preferred": true } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-01T01:53:24.928Z" } }, "status": { "code": 200, "name": "OK" } }