BRCA1 Circos: a visualisation resource for functional analysis of missense variants

Area of Science:

• Genetics and Genomics
• Cancer Biology
• Bioinformatics

Background:

• Germline mutations in the BRCA1 tumor suppressor gene increase breast and ovarian cancer risk.
• Over 1500 unique BRCA1 variants exist, classified as pathogenic, benign, or variants of unknown significance (VUS).
• Assessing the pathogenicity of VUS, often rare missense variants, requires functional assays due to unpredictable functional impact.

Purpose of the Study:

• To develop a visualization resource for functional data of all documented BRCA1 missense variants.
• To facilitate the analysis and interpretation of BRCA1 variants of unknown significance (VUS).

Main Methods:

• Developed BRCA1 Circos, a web-based visualization tool utilizing the Circos software package.
• Aggregated and harmonized functional study data for all published BRCA1 missense variants.
• Implemented search and interpretation functionalities for individual variant data.

Main Results:

• The BRCA1 Circos tool compiles and displays functional data for numerous BRCA1 missense variants.
• The resource aggregates data from various functional studies, presenting harmonized results.
• Provides functionalities for searching and interpreting individual BRCA1 missense variant functional information.

Conclusions:

• The BRCA1 Circos web tool serves as a public, comprehensive reference for functionally assessed BRCA1 missense variants.
• This visualization resource will aid in meta-analyses of functional data.
• Improves the assessment of pathogenicity for BRCA1 variants of unknown significance (VUS).