title: Clinically Significant Unclassified Variants inBRCA1andBRCA2genes among Korean Breast Cancer Patients.
abstract: OBJECTIVE
  Unclassified variants (UVs) ofBRCA1andBRCA2genes are not defined as pathogenic for breast cancer, and their clinical significance currently remains undefined. Therefore, this study was conducted to identify potentially pathogenic UVs by comparing their prevalence between breast cancer patients and controls.
  
  
  METHODS
  A total of 328 breast cancer patients underwentBRCA1/2genetic screening at the National Cancer Center of Korea. Genetic variants ofBRCAgenes that were categorized as unclassified according to the Breast Cancer Information Core database were selected based on allelic frequency, after which candidate variants were genotyped in 421 healthy controls. We also examined family members of the study participants. Finally, the effects of amino acid substitutions on protein structure and function were predictedin silico.
  
  
  RESULTS
  Genetic tests revealed 33 UVs inBRCA1and 47 inBRCA2. Among 15 candidates genotyped in healthy controls, c.5339T>C in BRCA1 and c.6029T>G, c.7522G>A in BRCA2 were not detected. Moreover, the c.5339T>C variant in theBRCA1gene was detected in four patients with a family history of breast cancer. This nonsynonymous variant (Leu1780Pro) in the BRCA1 C-terminal domain was predicted to have an effect on BRCA1 protein structure/function.
  
  
  CONCLUSIONS
  This study showed that comparison of genotype frequency between cases and controls could help identify UVs ofBRCAgenes that are potentially pathogenic. Moreover, ourfindings suggest that c.5339T>C inBRCA1might be a pathogenic variant for patients and their families.
authors.affiliation: Center for Breast Cancer, Hospital, National Cancer Center, Goyang, Korea.|College of Veterinary Medicine, Konkuk University, Seoul, Korea.
authors.forename: Kyong-Ah
authors.initials: KA
authors.lastname: Yoon
authors.affiliation: Department of Cancer Control and Policy, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
authors.forename: Boyoung
authors.initials: B
authors.lastname: Park
authors.affiliation: Biomolecular Function Research Branch, National Cancer Center, Goyang, Korea.
authors.forename: Byung Il
authors.initials: BI
authors.lastname: Lee
authors.affiliation: Center for Breast Cancer, Hospital, National Cancer Center, Goyang, Korea.
authors.forename: Moon Jung
authors.initials: MJ
authors.lastname: Yang
authors.affiliation: Genetic Counseling Clinic, Hospital, National Cancer Center, Goyang, Korea.|Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.|Translational Epidemiology Branch, National Cancer Center, Goyang, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kong
authors.affiliation: Center for Breast Cancer, Hospital, National Cancer Center, Goyang, Korea.|Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.|Precision Medicine Branch, Research Institute, National Cancer Center, Goyang, Korea.
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008403:Mass Screening; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D010375:Pedigree; D056910:Republic of Korea / Q000453:epidemiology; D012306:Risk; D014178:Translocation, Genetic
keywords: BRCA1; BRCA2; Familial breast cancer; Unclassified variants