Characterization of spliceogenic variants located in regions linked to high levels of alternative splicing: BRCA2 c.7976+5G > T as a case study.
Hum Mutat
; 39(9): 1155-1160, 2018 09.
Article
in En
| MEDLINE
| ID: mdl-29969168
ABSTRACT
Many BRCA1 and BRCA2 (BRCA1/2) genetic variants have been studied at mRNA level and linked to hereditary breast and ovarian cancer due to splicing alteration. In silico tools are reliable when assessing variants located in consensus splice sites, but we may identify variants in complex genomic contexts for which bioinformatics is not precise enough. In this study, we characterize BRCA2 c.7976 + 5G > T variant located in intron 17 which has an atypical donor site (GC). This variant was identified in three unrelated Spanish families and we have detected exon 17 skipping as the predominant transcript occurring in carriers. We have also detected several isoforms (Δ16-18, Δ17,18, Δ18, and â¼17q224 ) at different expression levels among carriers and controls. This study remarks the challenge of interpreting genetic variants when multiple alternative isoforms are present, and that caution must be taken when using in silico tools to identify potential spliceogenic variants located in GC-AG introns.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Alternative Splicing
/
BRCA2 Protein
/
Hereditary Breast and Ovarian Cancer Syndrome
/
Mutation
Type of study:
Prognostic_studies
Limits:
Aged
/
Aged80
/
Female
/
Humans
Language:
En
Journal:
Hum Mutat
Journal subject:
GENETICA MEDICA
Year:
2018
Type:
Article
Affiliation country:
Spain