Clinical Genome and Ancestry Report (CGAR)

Clinical Genome and Ancestry Report (CGAR) prioritizes and organizes clinically implicated genetic variants from genome sequencing to support interpretation using genotype-derived ancestral composition and matched-population allele frequencies.

Key Features:

• Organization into seven clinical categories: Organizes variants into seven distinct categories aligned with established clinical workflows.
• Reported Disease-Associated Variants: Identifies variants previously documented as linked to specific diseases.
• Rare- and High-Impact Variants in Putative Disease-Associated Genes: Detects rare, potentially high-impact variants within genes suspected of disease association.
• Secondary Findings (ACMG): Flags findings recommended for return by the American College of Medical Genetics and Genomics (ACMG).
• Actionable Pharmacogenomic Variants: Highlights variants with known implications for drug response and pharmacogenomic actionability.
• Focused Reports for Candidate Genes: Generates detailed reports centered on user-specified candidate genes.
• De Novo Variant Candidates for Trio Analysis: Identifies candidate de novo mutations present in an offspring and absent in parents.
• Germline and Somatic Variants for Cancer: Identifies germline and somatic variants implicated in cancer risk, diagnosis, treatment, and prognosis.
• Integration with genotype-derived ancestral composition: Integrates genotype-derived ancestry and highlights allele frequencies from matched populations to inform population-specific interpretation.
• External database linkage: Provides comprehensive external links to variant-centric and phenotype databases for further exploration and validation.

Scientific Applications:

• Clinical variant prioritization: Prioritizes variants from genome sequencing for clinical interpretation and reporting.
• Variant discovery in candidate genes: Supports detection of rare and high-impact variants in putative disease-associated genes for research and diagnosis.
• ACMG secondary findings reporting: Identifies and flags secondary findings recommended by ACMG for clinical disclosure.
• Pharmacogenomic-guided therapy: Enables identification of actionable pharmacogenomic variants to inform drug-response considerations.
• Trio-based de novo mutation analysis: Facilitates identification of de novo variant candidates in trio analyses for genetic disorder diagnosis.
• Cancer genomics interpretation: Assesses germline and somatic variants relevant to cancer risk assessment, diagnosis, treatment selection, and prognosis.
• Ancestry-aware allele frequency interpretation: Uses genotype-derived ancestry and matched-population allele frequencies to contextualize variant prevalence across populations.

Methodology:

Organizes variants into seven clinical categories, identifies rare/high-impact and de novo candidates, integrates genotype-derived ancestral composition to highlight matched-population allele frequencies, flags ACMG secondary findings and cancer-relevant germline/somatic variants, highlights actionable pharmacogenomic variants, generates focused candidate-gene reports, and links variants to external variant-centric and phenotype databases.