{ "observedDate": "2026-09-11", "variant": { "query": "NM_007294.4:c.68_69del", "identity": { "assembly": "GRCh38", "chromosome": "chr17", "position": 43124027, "reference": "ACT", "alternate": "A", "variant_type": "DEL", "canonical_key": "GRCh38:chr17:43124027:ACT:A" }, "recordUrl": "https://folklore.helena.bio/variant?assembly=GRCh38&chromosome=chr17&position=43124027&reference=ACT&alternate=A", "annotation": { "gene_symbol": "BRCA1", "gene_id": "ENSG00000012048", "transcript_id": "ENST00000357654", "consequence": "frameshift_variant", "impact": "HIGH", "biotype": "protein_coding", "exon_number": "2/23", "domains": [ "CDD:cd16498", "ENSP_mappings:1jm7", "ENSP_mappings:7jzv", "ENSP_mappings:7lyb", "ENSP_mappings:8grq", "ENSP_mappings:AF", "Gene3D:3", "PANTHER:PTHR13763", "PIRSF:PIRSF001734", "Superfamily:SSF57850" ] }, "display": { "label": "chr17:43124027 ACT>A", "hgvs_genomic": "chr17:g.43124030_43124031del", "hgvs_cdna": "ENST00000357654.9:c.68_69del", "hgvs_protein": "ENSP00000350283.3:p.Glu23ValfsTer17" }, "classification": { "framework": "acmg_2015", "automated_class": "P", "criteria": "PVS1,PS1,BS1_Strong[VCEP][af_grpmax] [VCEP:ENIGMA BRCA1/2 v1.2.0] [ERepo:ENIGMA BRCA1 and BRCA2 VCEP,BRCA1-related cancer predisposition]", "confidence_score": 0.8500000238418579, "pm1_evidence_source": null, "pm1_evidence_availability": "not_applicable" }, "clinvar": { "clinical_significance": "Pathogenic", "review_status": "reviewed_by_expert_panel", "review_stars": 3, "variation_id": "17662", "rsid": "80357914", "disease_names": [ "BRCA1-related_cancer_predisposition", "BRCA1-related_disorder", "Breast-ovarian_cancer,_familial,_susceptibility_to,_1", "Breast_and/or_ovarian_cancer", "Endometrial_carcinoma", "Familial_cancer_of_breast", "Fanconi_anemia,_complementation_group_S", "Hereditary_breast_ovarian_cancer_syndrome", "Hereditary_cancer-predisposing_syndrome", "Inherited_breast_cancer_and_ovarian_cancer", "Inherited_ovarian_cancer_(without_breast_cancer)", "Invasive_medullary_breast_carcinoma", "Malignant_tumor_of_breast", "Ovarian_neoplasm", "Pancreatic_cancer,_susceptibility_to,_4", "Triple-negative_breast_cancer", "not_provided" ], "protein_representation": null, "canonical_url": "https://www.ncbi.nlm.nih.gov/clinvar/variation/17662/", "availability": "available" }, "population": { "global_allele_frequency": 0.0001184799984912388, "global_allele_count": 191, "global_allele_number": 1612084, "homozygote_count": 0, "group_max_allele_frequency": 0.0001645279990043491, "popmax_population": "nfe", "rsid": "80357914", "canonical_url": "https://gnomad.broadinstitute.org/variant/chr17-43124027-ACT-A?dataset=gnomad_r4", "availability": "available" }, "availability": { "clinvar": "available", "expert": "available", "predictors": "no_record", "spliceai": "no_record", "conservation": "no_record", "gene_constraints": "available", "dosage": "available", "population": "available" }, "provenance": { "annotation_source": "vep_cache", "vep_version": "113", "vep_cache_version": "ensembl-vep-113-mane-v2", "reference_assembly": "GRCh38", "classifier_version": "3.39.1", "classifier_version_label": "v3.39.1", "reference_versions": [ { "name": "clingen_dosage", "version": "2026-01" }, { "name": "clingen_gdv", "version": "2026-01" }, { "name": "clinvar", "version": "2026-01" }, { "name": "dbnsfp", "version": "4.9c" }, { "name": "ensembl_vep", "version": "Release 113" }, { "name": "erepo_classifications", "version": "erepo-2026-06-04" }, { "name": "exon_pext", "version": "2.1.1" }, { "name": "g2p", "version": "2026-01" }, { "name": "gnomad", "version": "4.1" }, { "name": "gnomad_constraint", "version": "4.1" }, { "name": "gof_genes", "version": "2026-01" }, { "name": "hpo", "version": "2026-01" }, { "name": "interpro_pfam", "version": "2026-03" }, { "name": "mane_select", "version": "2.0" }, { "name": "mt_apogee2_scores", "version": "APOGEE2 v2.0" }, { "name": "mt_clinvar_variants", "version": "ClinVar 2026-01 (mtDNA subset)" }, { "name": "mt_gene_coordinates", "version": "rCRS NC_012920.1" }, { "name": "mt_haplogroups", "version": "PhyloTree Build 17 (FU1a)" }, { "name": "mt_helix_curated", "version": "(empty -- clinician-populated via PR-6 UI)" }, { "name": "mt_population_frequencies", "version": "MITOMAP 2026-01 + HelixMTdb 20200327" }, { "name": "nuclear_numt_known_regions", "version": "Calabrese 2017 + Dayama 2014" }, { "name": "orphanet", "version": "2025-12" }, { "name": "pubmed", "version": "(real-time)" }, { "name": "spliceai", "version": "1.3" }, { "name": "vcep_specs", "version": "2026-03" } ], "annotation_resolved": true, "classification_completed": true } }, "gene": { "contractVersion": "1.0", "status": "ok", "query": { "kind": "gene", "value": "FBN1", "match": "exact" }, "associations": [ { "geneSymbol": "FBN1", "hgncId": "HGNC:3603", "diseaseName": "Marfan syndrome", "diseaseId": "MONDO:0007947", "modeOfInheritance": "AD", "modeOfInheritanceId": "HP:0000006", "classification": "Definitive", "expertPanel": "General Gene Curation Expert Panel", "reportUrl": "https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_d3fc0bea-4d6e-449e-885c-b204e6a0b2bf-2019-03-04T170000.000Z", "classificationDate": "2019-03-04", "sopVersion": "SOP6" }, { "geneSymbol": "FBN1", "hgncId": "HGNC:3603", "diseaseName": "Shprintzen-Goldberg syndrome", "diseaseId": "MONDO:0008426", "modeOfInheritance": "AD", "modeOfInheritanceId": "HP:0000006", "classification": "Disputed", "expertPanel": "Intellectual Disability and Autism Gene Curation Expert Panel", "reportUrl": "https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_42caf14d-6400-475b-88f3-a8a24a0832c0-2021-12-01T110000.000Z", "classificationDate": "2021-12-01", "sopVersion": "SOP9" }, { "geneSymbol": "FBN1", "hgncId": "HGNC:3603", "diseaseName": "familial thoracic aortic aneurysm and aortic dissection", "diseaseId": "MONDO:0019625", "modeOfInheritance": "AD", "modeOfInheritanceId": "HP:0000006", "classification": "Definitive", "expertPanel": "Heritable Thoracic Aortic Aneurysm and Dissection Gene Curation Expert Panel", "reportUrl": "https://search.clinicalgenome.org/kb/gene-validity/CGGCIEX:assertion_8251", "classificationDate": "2017-01-23", "sopVersion": "SOP4" } ], "pagination": { "limit": 5, "offset": 0, "total": 3, "nextOffset": null }, "source": { "name": "ClinGen Gene-Disease Validity", "version": "clingen_gdv_2026-03-16.csv (ClinGen GDV export, FILE CREATED 2026-03-16)", "snapshotSha256": "0afcebafc4281280db5aa05e44588fb7bbf4217a2ed81bec83e55ee2c702052a", "downloadUrl": "https://search.clinicalgenome.org/kb/gene-validity/download", "license": "CC0-1.0", "attribution": "Gene-Disease Validity classifications obtained from the Clinical Genome Resource (ClinGen). Source version identifies the local reference export; it is not a claim of current upstream freshness." }, "warnings": [ "Reference assertions are not a diagnosis or variant classification. Coverage is limited to this ClinGen snapshot; missing associations do not establish absence. Distinct diseases and all evidence classifications are retained." ], "usage_boundary": { "intended_use": "professional_gene_disease_review", "patient_context_evaluated": false, "review_required": true, "not_for": [ "patient_diagnosis", "treatment_decision", "variant_pathogenicity_classification" ] } } }