SwePub
Tyck till om SwePub Sök här!
Sök i LIBRIS databas

  Extended search

WFRF:(Spurdle Amanda B.)
 

Search: WFRF:(Spurdle Amanda B.) > De la Hoya Miguel > Alternative splicin...

Alternative splicing and ACMG-AMP-2015-based classification of PALB2 genetic variants : An ENIGMA report

Lopez-Perolio, Irene (author)
Hospital Clinico San Carlos de Madrid
Leman, Raphaël (author)
Centre François Baclesse
Behar, Raquel (author)
Hospital Clinico San Carlos de Madrid
show more...
Lattimore, Vanessa (author)
University of Otago
Pearson, John F. (author)
University of Otago
Castéra, Laurent (author)
Centre François Baclesse
Martins, Alexandra (author)
University of Rouen
Vaur, Dominique (author)
Centre François Baclesse
Goardon, Nicolas (author)
Centre François Baclesse
Davy, Grégoire (author)
Centre François Baclesse
Garre, Pilar (author)
Hospital Clinico San Carlos de Madrid
García-Barberán, Vanesa (author)
Hospital Clinico San Carlos de Madrid
Llovet, Patricia (author)
Pérez-Segura, Pedro (author)
Hospital Clinico San Carlos de Madrid
Díaz-Rubio, Eduardo (author)
Hospital Clinico San Carlos de Madrid
Caldés, Trinidad (author)
Hospital Clinico San Carlos de Madrid
Hruska, Kathleen S. (author)
Hsuan, Vickie (author)
Wu, Sitao (author)
Pesaran, Tina (author)
Karam, Rachid (author)
Vallon-Christersson, Johan (author)
Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
Borg, Ake (author)
Skåne University Hospital
Investigators, Kconfab (author)
University of Melbourne,Peter MacCallum Cancer Centre
Valenzuela-Palomo, Alberto (author)
Velasco, Eladio Andrés (author)
Southey, Melissa (author)
University of Melbourne
Vreeswijk, Maaike P.G. (author)
Leiden University Medical Centre
Devilee, Peter (author)
Leiden University Medical Centre
Kvist, Anders (author)
Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
Spurdle, Amanda B. (author)
QIMR Berghofer Medical Research Institute
Walker, Logan C. (author)
University of Otago
Krieger, Sophie (author)
Centre François Baclesse
De La Hoya, Miguel (author)
Hospital Clinico San Carlos de Madrid
show less...
 (creator_code:org_t)
2019-03-19
2019
English.
In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 56:7, s. 453-460
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • Background: PALB2 monoallelic loss-of-function germ-line variants confer a breast cancer risk comparable to the average BRCA2 pathogenic variant. Recommendations for risk reduction strategies in carriers are similar. Elaborating robust criteria to identify loss-of-function variants in PALB2 - without incurring overprediction - is thus of paramount clinical relevance. Towards this aim, we have performed a comprehensive characterisation of alternative splicing in PALB2, analysing its relevance for the classification of truncating and splice site variants according to the 2015 American College of Medical Genetics and Genomics-Association for Molecular Pathology guidelines. Methods: Alternative splicing was characterised in RNAs extracted from blood, breast and fimbriae/ovary-related human specimens (n=112). RNAseq, RT-PCR/CE and CloneSeq experiments were performed by five contributing laboratories. Centralised revision/curation was performed to assure high-quality annotations. Additional splicing analyses were performed in PALB2 c.212-1G>A, c.1684+1G>A, c.2748+2T>G, c.3113+5G>A, c.3350+1G>A, c.3350+4A>C and c.3350+5G>A carriers. The impact of the findings on PVS1 status was evaluated for truncating and splice site variant. Results: We identified 88 naturally occurring alternative splicing events (81 newly described), including 4 in-frame events predicted relevant to evaluate PVS1 status of splice site variants. We did not identify tissue-specific alternate gene transcripts in breast or ovarian-related samples, supporting the clinical relevance of blood-based splicing studies. Conclusions: PVS1 is not necessarily warranted for splice site variants targeting four PALB2 acceptor sites (exons 2, 5, 7 and 10). As a result, rare variants at these splice sites cannot be assumed pathogenic/likely pathogenic without further evidences. Our study puts a warning in up to five PALB2 genetic variants that are currently reported as pathogenic/likely pathogenic in ClinVar.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

acmg-amp guidelines
palb2
pvs1
splicing
variant classification

Publication and Content Type

art (subject category)
ref (subject category)

Find in a library

To the university's database

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view