The significance of the BRCA2 c.9934A>G variant is really unknown?A series of patients with BRCA2 c.9934A>G variant among Çanakkale patients

Akcan M. B., Çelik K. M., Sılan F.

European Biotechnology Congress, Praha, Czech Republic, 5 - 07 October 2022, pp.48

  • Publication Type: Conference Paper / Summary Text
  • City: Praha
  • Country: Czech Republic
  • Page Numbers: pp.48
  • Çanakkale Onsekiz Mart University Affiliated: Yes


The  BRCA2  c.9934A>G(p.I3312V) (NM_000059.4) variant is classified as “Variant-of-Uncertain-Significance(VOUS)” according to ACMG criteria and found extremely low frequency in Gnomad population databases. In this case series, we aimed to raise the question that this variant may be pathogenic. After DNA isolation from peripheral blood, all exonic, exon-intron junctions of  BRCA2  were analyzed using the inherited cancer NGS panel method in 519 patients with cancer and/or familial cancer history. 6 patients had the BRCA2 c.9934A>G variant in a heterozygous state. Patient 1-3, had breast cancer (20-47-51 years-old), Patient 4, 42-years-old ovarian cancer, Patient 5 and 6, have a family history of pancreas and breast cancer respectively (40-56 years- old). BRCA2 is a human tumor suppressor gene involved in the repair of chromosomal damage. Therefore, its pathogenic mutations confer an increased risk of cancers such as breast, ovarian, pancreas, etc. Our data revealed the c.9934A>G variant in the BRCA2 gene in 6 patients. Detection of this variant only in patients with personal and/or family history of BRCA2-related-cancers seems far from coincidental. We think that this variant may be pathogenic due to the clinical conditions and strong family histories of the patients.Larger cohorts would be useful to elucidate the pathogenicity of this variant.