Chapter 13: Building an Automated Clinical NGS Variant Reporting Pipeline

Chapter 13: Building an Automated Clinical NGS Variant Reporting Pipeline

In this final capstone chapter, we engineer a production-ready, automated clinical reporting pipeline that ingests a patient's raw VCF file and outputs an audit-trailed, formatted Clinical Molecular Diagnostic Report ready for pathology sign-out.

1. Automated Clinical Report Generator in Python

import datetime
import json

def generate_clinical_report(patient_id: str, gene: str, hgvs_c: str, hgvs_p: str, acmg_class: str, criteria: list):
    report_date = datetime.date.today().strftime("%B %d, %Y")
    
    report_text = f\"\"\"
========================================================================================
                      CLINICAL MOLECULAR GENETICS LABORATORY REPORT
========================================================================================
PATIENT ID: {patient_id}                            REPORT DATE: {report_date}
TEST PERFORMED: Comprehensive Clinical Exome Panel  ASSAY VERSION: v2.5 (CLIA-Certified)
----------------------------------------------------------------------------------------
PRIMARY DIAGNOSTIC FINDING:
Gene:               {gene}
Transcript:         NM_000059.4
cDNA Change:        {hgvs_c}
Protein Change:     {hgvs_p}
Zygosity:           Heterozygous
Classification:     {acmg_class.upper()}
----------------------------------------------------------------------------------------
EVALUATION OF ACMG/AMP EVIDENCE CRITERIA:
{json.dumps(criteria, indent=4)}

INTERPRETATION SUMMARY:
The identified variant in {gene} ({hgvs_c}, {hgvs_p}) results in a premature termination
codon and loss of functional domains. Pathogenicity is supported by absence in gnomAD
controls and documented segregation in multiple affected pedigree lineages.

RECOMMENDATIONS:
1. Genetic counseling is strongly advised for the patient and at-risk family members.
2. Consider cascade testing for first-degree biological relatives.
========================================================================================
\"\"\"
    return report_text

# Example generation for a BRCA2 pathogenic variant
report = generate_clinical_report(
    patient_id="PT-2026-9812",
    gene="BRCA2",
    hgvs_c="c.5946delT",
    hgvs_p="p.Ser1982ArgfsTer22",
    acmg_class="Pathogenic",
    criteria=["PVS1 (Frameshift in LoF gene)", "PM2 (Absent in gnomAD)", "PP5 (ClinVar 3-Star Pathogenic)"]
)
print(report)