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WGS Cancer Gene Variant Analysis

Whole-genome sequencing (WGS) data analysis for pathogenic mutations in cancer predisposition genes.

Project Structure

.
├── your_file.vcf.gz          # Raw WGS VCF (DeepVariant v1.5.0, GRCh37)
├── src/
│   └── analyze.py            # VEP annotation pipeline script
├── BRCA2/
├── TP53/
├── RB1/
├── APC/
├── PTEN/
├── KRAS/
├── EGFR/
├── ATM/
├── CHEK2/
├── PALB2/
├── NAFLD/
├── NAFLD_extended/
└── CLINICAL_REPORT/       # Consolidated clinical-style summary (EN + zh-TW)

Each gene folder contains README.md (English) and README_zh-TW.md (Traditional Chinese).

Clinical Report

A consolidated, clinical-style summary of all findings is available in CLINICAL_REPORT/:

  • index.md — landing page with headline findings
  • cancer.md — 10-gene hereditary cancer screen (negative)
  • nafld.md — NAFLD/metabolic panel (high genetic risk; APOE ε4/ε4)

Each report follows a clinical structure: Specimen & Method → Results → Interpretation → Limitations → Recommendations → Considerations for Your Clinician. Recommendations are generic referrals; Considerations are data-framed observations, not medical directives.

Gene Analyses

Gene Chromosome Region (GRCh37) PASS Variants Coding Variants Pathogenic
BRCA2 chr13 32,889,611–32,973,805 68 2 (both benign) None
TP53 chr17 7,571,720–7,590,868 38 0 None
RB1 chr13 48,877,887–49,056,122 226 0 None
APC chr5 112,073,554–112,181,936 164 1 (benign) None
PTEN chr10 89,622,870–89,731,687 35 0 None
KRAS chr12 25,357,723–25,403,870 84 0 None
EGFR chr7 55,086,714–55,324,313 359 1 (benign) None
ATM chr11 108,093,211–108,239,829 55 1 (benign) None
CHEK2 chr22 29,083,731–29,138,410 108 0 None
PALB2 chr16 23,614,488–23,652,631 13 0 None

No pathogenic mutations detected across all 10 genes.

NAFLD Risk Variants Check

Gene rsID Location (GRCh37) Variant Genotype Result
PNPLA3 rs738409 chr22:44324727 I148M (C>G) HOM (G/G) Homozygous risk allele ×2
TM6SF2 rs58542926 chr19:19379549 E167K (C>T) HOM (T/T) Homozygous risk allele ×2
MBOAT7 rs641738 chr19:54676763 T>C (intronic) HET (C/T) Heterozygous risk allele ×1
HSD17B13 rs72613567 chr4:88231394 TA-insertion wild-type No protective allele

High NAFLD genetic risk profile — homozygous PNPLA3 I148M and TM6SF2 E167K, plus heterozygous MBOAT7. See NAFLD/ for full details.

Extended NAFLD Panel (GCKR, MTARC1, APOE, LYPLAL1, GPAM, PNPLA2, CIDEB, TRIB1, MERTK, PEMT)

Gene rsID Variant Genotype Result
GCKR rs1260326 P446L HET (T/C) Risk-modifier (population-dependent)
MTARC1 rs2642438 A165T HOM (G/G) Protective ×2 (favourable)
APOE rs429358+rs7412 ε2/ε3/ε4 ε4/ε4 Homozygous ε4 — clinically relevant
LYPLAL1 rs12137855 C>T wild-type No risk allele
GPAM rs2792751 I43V wild-type No risk allele
PNPLA2 rs1138693 L481P HET Common benign polymorphism
CIDEB (full gene scan) no coding variants No protective LoF variants
TRIB1 rs2954021/17321515/2954029 A>G/T wild-type No risk allele
MERTK rs34943572 N329S HET Rare, VUS
PEMT rs7946 V175M wild-type No risk allele

Notable: APOE ε4/ε4 (homozygous). See NAFLD_extended/ for full details.

Coding Variants Detail

Gene Variant (GRCh37) Genotype Protein ClinVar gnomAD AF Classification
BRCA2 chr13:32906729 A>C (rs144848) HET p.Asn372His Benign (expert panel) ~24% Common polymorphism
BRCA2 chr13:32929387 T>C (rs169547) HOM p.Val2466Ala Benign ~98% Near-fixed polymorphism
APC chr5:112176756 T>A HET p.Val2355Asp Not in ClinVar Low Likely benign
EGFR chr7:55229255 G>A HET p.Arg451Lys Not in ClinVar Common Common polymorphism
ATM chr11:108183167 A>G HOM p.Asn1497Ser Not in ClinVar Common Common polymorphism

Non-coding Variants Summary

Gene Total PASS Intronic UTR Upstream/Downstream Synonymous Splice-adjacent
BRCA2 68 ~50 ~5 ~10 3 0
TP53 38 ~25 ~1 ~12 0 0
RB1 226 ~180 ~20 ~25 0 1
APC 164 ~120 ~5 ~35 4 0
PTEN 35 ~25 ~3 ~7 0 0
KRAS 84 ~60 ~5 ~18 1 0
EGFR 359 ~280 ~15 ~50 4 0
ATM 55 ~40 ~5 ~10 0 1
CHEK2 108 ~85 ~5 ~18 0 0
PALB2 13 ~10 ~1 ~2 0 0

Method

  1. Extract PASS-quality variants from VCF using awk
  2. Annotate via Ensembl VEP REST API (GRCh37 HGVS endpoint)
  3. Cross-reference with ClinVar and gnomAD for clinical significance

Quick Run

python src/analyze.py <GENE> <CHROM> <START> <END> your_file.vcf.gz

Tools: bcftools, Python 3, Ensembl VEP REST API, NCBI E-utilities

Input

  • File: your_file.vcf.gz (173 MB)
  • Caller: DeepVariant v1.5.0
  • Reference: GRCh37 (hg19)
  • Sample: ULMEDCBB3A73_ULMEDCBB3A73

Tags

Tag Description
v1.0 Initial BRCA2 analysis
v1.1 Traditional Chinese README added
v1.2 Session export log added
v1.3 Docs reorganized into gene folders
TP53 TP53 analysis added
RB1 RB1 analysis added
APC APC analysis added
PTEN PTEN analysis added
KRAS KRAS analysis added
EGFR EGFR analysis added
ATM ATM analysis added
CHEK2 CHEK2 analysis added
PALB2 PALB2 analysis added
v2.0 Full 10-gene summary tables added
rc-1 Session export log added
NAFLD NAFLD core 4-locus panel
NAFLD_extended Extended NAFLD panel (10 loci)
NAFLD_corrected Core panel corrected (chr-prefix bug fix)
v3.0 Clinical report added (CLINICAL_REPORT/)

Disclaimer

This is a computational analysis, not a clinical-grade variant interpretation. For medical decisions, consult a certified genetic counselor or clinical genetics laboratory.

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Cancer Driver Genes check from my WGS vcf file

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