Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts

Hdl Handle:
http://hdl.handle.net/10147/239152
Title:
Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts
Authors:
Whiley, Phillip J; Pettigrew, Christopher A; Brewster, Brooke L; Walker, Logan C; kConFab Investigators; Spurdle, Amanda B; Brown, Melissa A
Citation:
BMC Medical Genetics. 2010 May 28;11(1):80
Issue Date:
28-May-2010
URI:
http://dx.doi.org/10.1186/1471-2350-11-80; http://hdl.handle.net/10147/239152
Abstract:
Abstract Background Genetic screening of breast cancer patients and their families have identified a number of variants of unknown clinical significance in the breast cancer susceptibility genes, BRCA1 and BRCA2. Evaluation of such unclassified variants may be assisted by web-based bioinformatic prediction tools, although accurate prediction of aberrant splicing by unclassified variants affecting exonic splice enhancers (ESEs) remains a challenge. Methods This study used a combination of RT-PCR analysis and splicing reporter minigene assays to assess five unclassified variants in the BRCA2 gene that we had previously predicted to disrupt an ESE using bioinformatic approaches. Results Analysis of BRCA2 c.8308 G > A (p.Ala2770Thr) by mRNA analysis, and BRCA2 c.8962A > G (p.Ser2988Gly), BRCA2 c.8972G > A (p.Arg2991His), BRCA2 c.9172A > G (p.Ser3058Gly), and BRCA2 c.9213G > T (p.Glu3071Asp) by a minigene assay, revealed no evidence for aberrant splicing. Conclusions These results illustrate the need for improved methods for predicting functional ESEs and the potential consequences of sequence variants contained therein.
Item Type:
Journal Article

Full metadata record

DC FieldValue Language
dc.contributor.authorWhiley, Phillip J-
dc.contributor.authorPettigrew, Christopher A-
dc.contributor.authorBrewster, Brooke L-
dc.contributor.authorWalker, Logan C-
dc.contributor.authorkConFab Investigators-
dc.contributor.authorSpurdle, Amanda B-
dc.contributor.authorBrown, Melissa A-
dc.date.accessioned2012-08-20T11:56:15Z-
dc.date.available2012-08-20T11:56:15Z-
dc.date.issued2010-05-28-
dc.identifier.citationBMC Medical Genetics. 2010 May 28;11(1):80-
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2350-11-80-
dc.identifier.urihttp://hdl.handle.net/10147/239152-
dc.description.abstractAbstract Background Genetic screening of breast cancer patients and their families have identified a number of variants of unknown clinical significance in the breast cancer susceptibility genes, BRCA1 and BRCA2. Evaluation of such unclassified variants may be assisted by web-based bioinformatic prediction tools, although accurate prediction of aberrant splicing by unclassified variants affecting exonic splice enhancers (ESEs) remains a challenge. Methods This study used a combination of RT-PCR analysis and splicing reporter minigene assays to assess five unclassified variants in the BRCA2 gene that we had previously predicted to disrupt an ESE using bioinformatic approaches. Results Analysis of BRCA2 c.8308 G > A (p.Ala2770Thr) by mRNA analysis, and BRCA2 c.8962A > G (p.Ser2988Gly), BRCA2 c.8972G > A (p.Arg2991His), BRCA2 c.9172A > G (p.Ser3058Gly), and BRCA2 c.9213G > T (p.Glu3071Asp) by a minigene assay, revealed no evidence for aberrant splicing. Conclusions These results illustrate the need for improved methods for predicting functional ESEs and the potential consequences of sequence variants contained therein.-
dc.titleEffect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts-
dc.typeJournal Article-
dc.language.rfc3066en-
dc.rights.holderPhillip J Whiley et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2012-08-20T11:07:33Z-
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