Scoring System
The Nephro Candidate Score (NCS) is a composite score (0–10) for prioritizing candidate variants in kidney disease research. It combines gene, variant, and inheritance evidence; it is not a calibrated probability of causality.
Score Components
1. Gene Score (0-1)
- Reflects nephrology relevance of the gene
- Based on known kidney disease associations
- Weight: 4x in final calculation
2. Variant Score (0-1)
- Summarizes variant evidence for prioritization
- Uses VEP consequence and impact annotations, CADD scores, and gnomAD population frequencies
- Weight: 4x in final calculation
3. Inheritance Score (0-1)
- Incorporates inheritance pattern and segregation evidence
- Includes penalty system for missing data
- Weight: 2x in final calculation
Final Calculation
NCS = (Gene Score × 4) + (Variant Score × 4) + (Inheritance Score × 2)Score Interpretation
| NCS Range | Priority | Description |
|---|---|---|
| 7 ≤ NCS ≤ 10 | High | Highest prioritization tier |
| 3 ≤ NCS < 7 | Moderate | Middle prioritization tier |
| 0 ≤ NCS < 3 | Low | Lowest prioritization tier |
Inheritance Patterns
Base Scores
| Pattern | Base Score |
|---|---|
| Denovo | 0.95 |
| Homozygous recessive | 0.8 |
| Compound heterozygous (confirmed) | 0.8 |
| X-linked recessive | 0.7 |
| X-linked dominant | 0.5 |
| Inherited dominant | 0.4 |
| Compound heterozygous (suspected) | 0.4 |
| Unknown | 0.1 |
Segregation Enhancement
For patterns with segregation data:
- Strong segregation evidence (p ≤ 0.001) provides maximum enhancement
- Enhancement factor calculated using logarithmic transformation
- Missing segregation data multiplies the inheritance component by 0.8 for applicable patterns; it does not reduce the entire NCS by 20%
Zero is valid segregation input. The Denovo, Unknown, and Compound heterozygous (suspected) patterns do not receive a missing-segregation penalty.
Best Practices
- Always provide segregation data when available for inherited patterns
- Use "Denovo" for confirmed de novo variants (no segregation needed)
- Interpret scores in context with clinical judgment
For detailed mathematical formulas and examples, see the comprehensive scoring documentation.