Abstract

Background: Next-generation sequencing has been leading the genetic study of human disease for the past 10 years, generating a huge amount of sequence variant data, which are stored in variant call format (VCF) files. The aim of the study was to reassess the utility of VCF files for reanalysis.
Methodology: This is a descriptive observational study of Saudi patients with undiagnosed genetic conditions. VCF files from 20 samples were referred to the molecular laboratory by physicians for reanalysis using variant interpretation software.
Results: Seven cases (n = 20) have been reported differently from the outside laboratory. This accounts for almost 35% of all cases and is mainly due to the ability to gather more information about the patient's phenotype. One whole-genome sequence (WGS) case changed from inconclusive to negative. In addition, we identified variants related to the patient's phenotype in six cases; two of them were WGS and four were whole-exome sequence, all reported as negative before the reanalysis.
Conclusion: Comprehensive phenotyping of individuals is a crucial step in identifying candidate phenotype-related variants. We outline the benefit obtained from access to the patient's medical records and communication with referring physicians.

Key words: report, variants, vcf, reassessment, genomic, genetic, NGS