| { | |
| "title": "Mosaic Somatic vs Germline Allelic Stratification Matrix", | |
| "description": "Stratification of WGS variants by Variant Allele Frequency (VAF) and inferred cellular lineage distribution in patient tissues.", | |
| "bins": [ | |
| { | |
| "vaf_range": "5.0% \u2013 15.0%", | |
| "category": "Late Post-Zygotic Somatic Subclone", | |
| "inferred_timing": "Post-Gastrulation / Tissue-Specific Sublineage", | |
| "variant_count": 28, | |
| "mean_dp": "37.8\u00d7", | |
| "tissue_penetrance": "~10% \u2013 30% of diploid cells", | |
| "key_genes_affected": "MAD1L1, CEP192, SMC5, CENPE", | |
| "biological_impact": "Subclonal diversity; represents late mitotic nondisjunction events during regional organ expansion." | |
| }, | |
| { | |
| "vaf_range": "15.1% \u2013 28.0%", | |
| "category": "Intermediate Mesodermal Somatic Clone", | |
| "inferred_timing": "Blastocyst to Early Gastrula (E5\u2013E14)", | |
| "variant_count": 34, | |
| "mean_dp": "36.5\u00d7", | |
| "tissue_penetrance": "~30% \u2013 56% of diploid cells", | |
| "key_genes_affected": "BUB1B, MAD1L1, CEP192, TP53", | |
| "biological_impact": "Substantial mesodermal colonization; high risk for regional developmental anomalies and embryonal tumorigenesis." | |
| }, | |
| { | |
| "vaf_range": "28.1% \u2013 38.0%", | |
| "category": "Major Post-Zygotic Mosaic Driver", | |
| "inferred_timing": "First 2\u20134 Cleavage Divisions (2-cell to 8-cell morula)", | |
| "variant_count": 22, | |
| "mean_dp": "38.2\u00d7", | |
| "tissue_penetrance": "~56% \u2013 76% of diploid cells", | |
| "key_genes_affected": "TRIP13 (VAF=28.6%), BUB1B, CEP192, MAD1L1", | |
| "biological_impact": "Primary mosaic driver clone; present across all three germ layers with dominant penetrance in renal and muscular tissues." | |
| }, | |
| { | |
| "vaf_range": "40.0% \u2013 60.0%", | |
| "category": "Mendelian Germline Heterozygous", | |
| "inferred_timing": "Pre-Zygotic (Inherited from gametes) or Zygotic (t=0)", | |
| "variant_count": 924, | |
| "mean_dp": "36.1\u00d7", | |
| "tissue_penetrance": "100% of nucleated cells (1 allele per diploid cell)", | |
| "key_genes_affected": "BUB1B, CEP57, MAD1L1, WT1, DICER1, SMC5", | |
| "biological_impact": "Constitutive genetic background providing autosomal recessive susceptibility or compound heterozygosity." | |
| }, | |
| { | |
| "vaf_range": "85.0% \u2013 100.0%", | |
| "category": "Constitutive Homozygous Alternate", | |
| "inferred_timing": "Pre-Zygotic Homozygous Allele", | |
| "variant_count": 568, | |
| "mean_dp": "35.9\u00d7", | |
| "tissue_penetrance": "100% of nucleated cells (2 alleles per diploid cell)", | |
| "key_genes_affected": "CEP192, MAD1L1, BUB1, SMC5, CENPF", | |
| "biological_impact": "Fixed genomic polymorphisms or homozygous ancestral alleles across candidate loci." | |
| } | |
| ] | |
| } |