PATH-SCAN: a reporting tool for identifying clinically actionable variants.

Area of Science:

• Genomics
• Medical Genetics
• Bioinformatics

Background:

• The American College of Medical Genetics and Genomics (ACMG) has issued guidelines for reporting incidental findings in genetic sequencing.
• Direct-to-consumer (DTC) genetic testing and decreasing costs of whole exome/genome sequencing increase individual access to genomic data analysis.
• Individuals increasingly seek to interpret their own genetic information, necessitating tools for variant analysis.

Purpose of the Study:

• To develop and validate a web-based tool, PATH-SCAN, for annotating individual genomes and exomes.
• To identify ClinVar-designated pathogenic variants within genes recommended by ACMG guidelines.
• To facilitate the identification of potential risk variants for medical consultation and enable anonymous data submission for population frequency studies.

Main Methods:

• Development of a web-based tool, PATH-SCAN, for genomic data annotation.
• Annotation focused on ClinVar pathogenic variants within ACMG-specified genes.
• Testing the tool on diverse genomic datasets: 1000 Genomes Project (1092 genomes), Personal Genome Project (163 genomes), and a clinical research project (15 genomes).

Main Results:

• PATH-SCAN successfully annotated genomes for pathogenic variants.
• Excluding a common variant in the 1000 Genomes dataset, approximately 20% of all analyzed genomes harbored a ClinVar pathogenic variant requiring further medical evaluation.
• The tool demonstrated utility across publicly available and clinical genomic datasets.

Conclusions:

• PATH-SCAN provides a valuable resource for individuals and researchers to identify actionable genetic risk variants.
• The tool supports informed medical decision-making by highlighting potential health predispositions.
• PATH-SCAN facilitates population-level data collection on variant frequencies through anonymous submissions.