Genomic Variant Analysis Report

**Genomic Variant Analysis Report** **Case Identifier:** Case ID: GVA-2024-001, Sample Barcode: S123456, Accession Number: A78910, Analysis Setup: Trio **Gene(s) Involved:** Gene: BRCA1 (Breast Cancer 1), Transcript Version: NM_007294.3, Multiple Transcripts Assessed: Yes **Variant Description:** HGVS Nomenclature: c.5266dupC (p.Gln1756Profs*74), Genomic Coordinates: GRCh38 chr17:43044295, Variant Type: Frameshift, Allele State: Heterozygous **Sequencing and Quality Metrics:** Platform: Illumina, Depth of Coverage: 150x, Base Quality: High, Read Support: Both Strands, Mapping Quality: Excellent, Manual Review: Performed in IGV **Bioinformatic Assessment:** Predictive Tool Scores: PolyPhen: Probably Damaging, CADD: 35, SpliceAI: No Impact, Population Frequency: Absent in gnomAD, Gene Constraint: High, Evolutionary Conservation: Conserved, Software Versions: VEP v101, gnomAD v3.1 **Classification:** Classification Outcome: Pathogenic, Evidence Codes: PVS1 (Strong), PM2 (Moderate), PP3 (Supporting), Rationale: Frameshift variant leading to premature truncation, absent in population databases, predicted damaging by multiple tools **Literature and Database Evidence:** ClinVar Entry: RCV000031724, Submitter ID: SCV000061234, HGMD Entry: CM920000, Relevant Literature: Smith et al., 2020, Segregation Studies: Consistent with disease phenotype **Final Interpretation:** The BRCA1 variant c.5266dupC is associated with hereditary breast and ovarian cancer syndrome. The variant is heterozygous and correlates with the autosomal dominant inheritance pattern observed in the family history. Clinical causality is highly likely. **Recommendations:** - Confirmatory Sanger sequencing - Segregation testing in relatives - Submission to ClinVar - Discussion in MDT rounds