MVA Syndrome Multi-Dimensional Genomic Studio

MVA SYNDROME MULTI-DIMENSIONAL 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

Clinical & Phenomics clin_01_hpo_hierarchy 8 rows

HPO Term Ontological Hierarchy & Phenotypic Specificity

Detailed phenotypic depth, information content (IC), and syndromic specificity of proband HPO features.

📑 Table Discovery Matrix (Click any table card to load instantly):

📋 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

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

📋 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

🧪 ACMG / AMP Diagnostic Variant Pathogenicity Classification Table

Formal ACMG/AMP clinical evidence tiering of prioritized candidate mutations across Spindle Assembly Checkpoint and sarcoma driver loci.

Gene	HGVSc / Protein Change	Genomic Coordinate (GRCh38)	Ref → Alt	Variant Type	VAF	ACMG Evidence Criteria	gnomAD v4.1 AF	REVEL / CADD	Final ACMG Tier

💊 Precision Oncology & Therapeutic Target Matrix

Targeted therapies, synthetic lethality vulnerabilities, and investigational small molecules exploiting chromosomal instability (CIN) and mitotic spindle defects.

Drug / Small Molecule	Target Gene	Pharmacological Class	Mechanism of Action	Synergy with MVA Phenotype	Clinical Trial Status	Evidence Tier

⚡ 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

🔬 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 Quality Audit (4 Lanes)

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%

Comprehensive Lane-by-Lane Telemetry Audit

Lane ID	Read Pairs FASTQ Files	Total Size	Paired Reads	Q30 %	GC %	Est. Coverage	Dup Rate	Mapping Rate	Flowcell Status

⚙️ Spindle Assembly Checkpoint (SAC) & Centrosomal Protein Network

Mitotic Machinery

Multi-Omics Analytical Matrix Explorer