Variant-specific Mendelian Risk Prediction Model

Area of Science:

• Genetics and Genomics
• Cancer Epidemiology
• Biostatistics

Background:

• Pathogenic sequence variants (PSVs) are linked to increased cancer risk.
• Existing Mendelian risk models often assume uniform penetrance for all PSVs within a gene.
• This assumption is inaccurate for genes like BRCA1/2 where risk varies by specific variant.

Conclusions:

• Mendelian risk prediction models can be effectively extended to integrate variant-specific penetrance data.
• These enhanced models offer more precise PSV carrier probabilities, improving future cancer risk predictions.
• The approach is adaptable as more variant-specific penetrance information becomes available.