@article {37946,
	title = {Functional characterization of CHEK2 variants in a Saccharomyces cerevisiae system},
	journal = {Hum.Mutat.},
	volume = {40},
	year = {2019},
	note = {IS - 1098-1004 (Electronic)
IS - 1059-7794 (Linking)
LA - eng
PT - Journal Article
PT - Research Support, Non-U.S. Gov{\textquoteright}t
RN - EC 2.7.1.11 (Checkpoint Kinase 2)
RN - EC 2.7.11.1 (CHEK2 protein, human)
SB - IM},
	month = {2019/05//},
	pages = {631 - 648},
	abstract = {Genetic testing for cancer predisposition leads to the identification of a number of variants with uncertain significance. To some extent, variants of BRCA1/2 have been classified, in contrast to variants of other genes. CHEK2 is a typical example, in which a large number of variants of unknown clinical significance were identified and still remained unclassified. Herein, the CHEK2 variant assessment was performed through an in vivo, yeast-based, functional assay. In total, 120 germline CHEK2 missense variants, distributed along the protein sequence, and two large in-frame deletions were tested, originating from genetic test results in breast cancer families, or selected from the ClinVar database. Of these, 32 missense and two in-frame deletions behaved as non-functional, 73 as functional, and 15 as semi-functional, after comparing growth rates of each strain with positive and negative controls. The majority of non-functional variants were localized in the CHK2 kinase and forkhead-associated domains. In vivo results from the non-functional variants were in agreement with in silico predictions, and, where available, with strong breast cancer family history, to a great extent. The results of the largest, to date, yeast-based assay, evaluating CHEK2 variants, can complement and assist in the classification of rare CHEK2 variants with unclear clinical significance},
	keywords = {Alleles, Amino Acid Substitution, Checkpoint Kinase 2, Computational Biology, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, genetics, Greece, Humans, metabolism, methods, Models,Molecular, Mutation, Pedigree, Protein Conformation, Saccharomyces cerevisiae},
	url = {PM:30851065},
	author = {Delimitsou,A. and Fostira, F. and Kalfakakou,D. and Apostolou, P. and Konstantopoulou, I. and Kroupis, C. and Papavassiliou, A.G. and Kleibl,Z. and Stratikos,E. and Voutsinas, G.E. and Yannoukakos, D.}
}
