Identification of novel exonic variants contributing to hereditary breast and ovarian cancer in west Indian population

Gene. 2023 Feb 5:852:147070. doi: 10.1016/j.gene.2022.147070. Epub 2022 Nov 24.


Breast and ovarian cancers are the most common cancer types in females worldwide and in India. Patients with these cancers require an early diagnosis which is essential for better prognosis, treatment and improved patient survival. Recently, the utilization of next-generation sequencing (NGS)-based screening has accelerated molecular diagnosis of various cancers. In the present study, we performed whole-exome sequencing (WES) of 30 patients who had a first or second-degree relative with breast or ovarian cancer and are tested negative for BRCA1/2 or other high and moderate-risk genes reported for HBOC. WES data from patients were analyzed and variants were called using bcftools. Functional annotation of variants and variant prioritization was performed by Exomiser. The clinical significance of variants was determined as per ACMG classification using Varsome tool. The functional analysis of genes was determined by STRING analysis and disease association was determined by open target tool. We found novel variants and gene candidates having significant association with HBOC conditions. The genes identified by exomiser (phenotype score > 0.75) are associated with various biological processes such as DNA integrity maintenance, transcription regulation, cell cycle regulation, and apoptosis. Our findings provide novel and prevalent gene variants associated with the HBOC condition in the West Indian population which could be further studied for early diagnosis and better prognosis of HBOC.

Keywords: Autosomal dominant diseases; HBOC; Next-generation sequencing; Non-BRCA genes; Whole-exome sequencing.

MeSH terms

  • BRCA1 Protein / genetics
  • Breast Neoplasms* / genetics
  • Exons
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • India
  • Ovarian Neoplasms* / genetics


  • BRCA1 Protein