MVA SYNDROME 5D GENOMIC STUDIO
PROBAND: EX2312012 (HGWCNDSX7)
TOTAL WGS VARIANTS 5,012,204
CANDIDATE VARIANTS 1,576
MOSAIC CANDIDATES 84
MEAN COVERAGE 36.2× (NovaSeq)
PRIVATE DATASET LINKED

📋 Proband Case Summary & Diagnostic Context

Rare Disease: MVA Syndrome
Clinical Presentation: Pediatric patient presenting with a coherent phenotypic cluster of embryonal malignancy (rhabdomyosarcoma), congenital nephrocalcinosis, severe intrauterine growth restriction (IUGR), microcephaly/short stature, failure to thrive, and parental history of recurrent miscarriages.
Primary Oncological Event: Rhabdomyosarcoma (Soft Tissue Tumour)
Renal Anomalies: Congenital Nephrocalcinosis (Since Birth)
Gestational Age at Birth: 32 Weeks (Premature)
Birth Weight: ~1.0 kg (Severe IUGR / Small for Gestational Age)
Family Reproductive History: Parental Recurrent Spontaneous Abortions
Diagnostic Trigger: Urgent Whole Genome Sequencing (WGS)

💡 Syndromic Diagnostic Key:

In chromosomal instability syndromes such as Mosaic Variegated Aneuploidy (MVA), no single finding is isolated. The hallmark is the triad of growth restriction + pediatric cancer predisposition + chromosome segregation/mitotic checkpoint defects. Parental recurrent pregnancy loss further points to segregation/aneuploidy vulnerability.

🏷️ Human Phenotype Ontology (HPO) Profile

8 Phenotypes
Showing 0 / 0 variants
GENOME-WIDE CHROMOSOME DENSITY (Click chromosome to filter):
Gene Chromosome:Position Ref → Alt Type Genotype (GT) Allelic Depth (AD) Total DP VAF (Allele Fraction) Classification Filter Action

🔬 Variant Allele Frequency (VAF) Spectrum & Mosaicism Analysis

Somatic vs Germline Resolution

In Mosaic Variegated Aneuploidy, post-zygotic somatic mutations and mitotic nondisjunction events exhibit non-Mendelian allele frequencies. Variants with VAF between 5% and 38% (0.05 – 0.38) represent high-confidence mosaic somatic candidates.

MOSAIC SOMATIC SPECTRUM 5% – 38% VAF
GERMLINE HETEROZYGOUS 40% – 60% VAF
GERMLINE HOMOZYGOUS 85% – 100% VAF

⭐ Top Mosaic Somatic Candidate Loci

Prioritized SAC & Centrosome Mutants

📊 Illumina NovaSeq 6000 Flowcell Metrics

Flowcell ID: HGWCNDSX7
Total Sequencing Data 78.86 GB
Total Paired Reads 805.8 Million
Mean Genome Coverage 36.2×
Bases ≥ Q30 93.45%
Mean Insert Size 380 bp
Duplication Rate 8.4%

Lane-by-Lane Sequencing Breakdown (4 Flowcell Lanes)

Lane Read 1 (R1) FASTQ R1 Size Read 2 (R2) FASTQ R2 Size Total Reads Q30 % Est. Coverage

📋 Candidate Gene Burden & ACMG Pathogenicity Matrix

Comprehensive comparative matrix analyzing all 16 candidate genes in the patient across OMIM phenotypes, variant burdens, inheritance models, and diagnostic tiers.

Gene OMIM / Cytoband Syndromic Classification Mitotic Complex / Role Inheritance Proband Variants Highest VAF Mosaic Loci Clinical Presentation Link Diagnostic Tier

🩺 Proband Phenotype Constellation vs Syndromic Differential Matrix

Systematic cross-referencing of observed clinical HPO findings against competing pediatric cancer and primordial growth syndromes.

Clinical Feature (HPO) MVA Syndrome Match Implicated Candidate Genes Competing Syndromic Differentials Cellular & Molecular Mechanism Discriminatory Diagnostic Power

⚡ Mosaic Somatic vs Germline Allelic Stratification Table

Stratification of whole-genome variants by Variant Allele Frequency (VAF), developmental timing, and inferred tissue lineage penetrance.

VAF Range Classification & Timing Total Variants Mean Sequencing DP Estimated Lineage Penetrance Candidate Genes Affected Pathological & Aneuploidy Consequence

🔬 Mitotic Spindle Assembly Checkpoint & Centrosome Interactome Matrix

Biochemical, structural, and macromolecular properties of key mitotic proteins in the MVA syndrome network.

Protein (UniProt) Length Subcellular Location Biochemical Function & Activity Macromolecular Complex MVA Disease Association Proband WGS Findings

🌐 24-Chromosome Karyotype Architecture & Genomic Instability Matrix

Genome-wide breakdown of chromosomal physical lengths, variant densities, SNV/Indel ratios, and literature-reported MVA aneuploidy vulnerability rates.

Chromosome Length (GRCh38) Total Variants SNVs Indels Variant Density SNV/Indel Ratio Heterozygous / Homozygous Reported MVA Aneuploidy Vulnerability in Literature