English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Background  Pathogenic variants in  BRCA1  and  BRCA2  cause hereditary breast and ovarian cancer. Screening of these genes has become easily accessible in diagnostic laboratories. Sequencing and copy number analyses are used to detect pathogenic variants, but also lead to identification of variants of unknown clinical significance (VUS). If the effect of a VUS can be clarified, it has direct consequence for the clinical management of the patient and family members. A splicing assay is one of several tools that might help in the classification of VUS. We therefore established mRNA analyses for  BRCA1  and  BRCA2  in the diagnostic laboratory in 2015. We hereby report the results of mRNA analysis variants in  BRCA1  and  BRCA2  after three years.    Methods  Variants predicted to alter splicing and variants within the canonical splice sites were selected for splicing analyses. Splicing assays were performed by reverse transcription-PCR of patient RNA. A biallalic expression analysis was carried out whenever possible.    Results  Twenty-five variants in  BRCA1  and  BRCA2  were analyzed by splicing assays; nine showed altered transcripts and 16 showed normal splicing patterns. The two novel pathogenic variants in  BRCA1  c.4484 + 3 A > C and c.5407–10G > A were characterized.    Conclusions  We conclude that mRNA analyses are useful in characterization of variants that may affect splicing. The results can guide classification of variants from unknown clinical significance to pathogenic or benign in a diagnostic laboratory, and thus be of direct clinical importance.

Diagnostic mRNA splicing assay for variants in BRCA1 and BRCA2 identified two novel pathogenic splicing aberrations