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Functional redundancy of exon 12 of BRCA2 revealed by a comprehensive analysis of the c.6853A>G (p.I2285V) variant by Lili Li; Kajal Biswas; Laura Anne Habib; Sergey G. Kuznetsov; Nancy Hamel; Tomas Kirchhoff; Nora Wong; Susan Armel; George Chong; Steven A. Narod; Kathleen Claes; Kenneth Offit; Mark E. Robson; Stacey Stauffer; Shyam K. Sharan; William D. Foulkes is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Functional redundancy of exon 12 of BRCA2 revealed by a comprehensive analysis of the c.6853A>G (p.I2285V) variant about?

Variants of unknown significance (VUS) in BRCA1 and BRCA2 are common, and present significant challenges for genetic counseling. We observed that BRCA2: c.6853A4G (p.I2285V) (Breast Cancer Information Core [BIC] name: 7081A4G; http://research. nhgri.nih.gov/bic/) co-occurs in trans with the founder mutation c.5946delT (p.S1982RfsX22) (BIC name: 6174delT), supporting the published classification of p.I2285V as a neutral variant. However, we also noted that when compared with wild-type BRCA2, p.I2285V resulted in increased exclusion of exon 12. Functional assay using allelic complementation in Brca2-null mouse embryonic stem cells revealed that p.I2285V, an allele with exon 12 deleted and wild-type BRCA2 were all phenotypically indistinguishable, as measured by sensitivity to DNA-damaging agents, effect on irradiation-induced Rad51 foci formation, homologous recombination, and overall genomic integrity. An allele frequency study showed the p.I2285V variant was identified in 15 out of 722 (2.1%) Ashkenazi Jewish cases and 10 out of 475 (2.1%) ethnically-matched controls (odds ratio, 0.99; 95% confidence interval: 0.44-2.21; P 5 0.97). Thus the p.I2285V variant is not associated with a

Who reads Functional redundancy of exon 12 of BRCA2 revealed by a comprehensive analysis of the c.6853A>G (p.I2285V) variant?

Author

Lili Li; Kajal Biswas; Laura Anne Habib; Sergey G. Kuznetsov; Nancy Hamel; Tomas Kirchhoff; Nora Wong; Susan Armel; George Chong; Steven A. Narod; Kathleen Claes; Kenneth Offit; Mark E. Robson; Stacey Stauffer; Shyam K. Sharan; William D. Foulkes

Publisher

Hindawi Limited

Published

2009

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)