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Clinical, splicing,...
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Thomassen, MadsOdense University Hospital
(author)
Clinical, splicing, and functional analysis to classify BRCA2 exon 3 variants : Application of a points-based ACMG/AMP approach
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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2022-10-23
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Hindawi Limited,2022
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24 s.
Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:171bb2ac-6d6f-4e70-b3bd-ef4481a955c7
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https://lup.lub.lu.se/record/171bb2ac-6d6f-4e70-b3bd-ef4481a955c7URI
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https://doi.org/10.1002/humu.24449DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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Skipping of BRCA2 exon 3 (∆E3) is a naturally occurring splicing event, complicating clinical classification of variants that may alter ∆E3 expression. This study used multiple evidence types to assess pathogenicity of 85 variants in/near BRCA2 exon 3. Bioinformatically predicted spliceogenic variants underwent mRNA splicing analysis using minigenes and/or patient samples. ∆E3 was measured using quantitative analysis. A mouse embryonic stem cell (mESC) based assay was used to determine the impact of 18 variants on mRNA splicing and protein function. For each variant, population frequency, bioinformatic predictions, clinical data, and existing mRNA splicing and functional results were collated. Variant class was assigned using a gene-specific adaptation of ACMG/AMP guidelines, following a recently proposed points-based system. mRNA and mESC analysis combined identified six variants with transcript and/or functional profiles interpreted as loss of function. Cryptic splice site use for acceptor site variants generated a transcript encoding a shorter protein that retains activity. Overall, 69/85 (81%) variants were classified using the points-based approach. Our analysis shows the value of applying gene-specific ACMG/AMP guidelines using a points-based approach and highlights the consideration of cryptic splice site usage to appropriately assign PVS1 code strength.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Mesman, Romy L.S.Leiden University Medical Centre
(author)
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Hansen, Thomas V.O.Copenhagen University Hospital
(author)
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Menendez, MireiaCatalan Institute of Oncology
(author)
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Rossing, MariaCopenhagen University Hospital
(author)
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Esteban-Sánchez, AdaHospital Clinico San Carlos de Madrid
(author)
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Tudini, EmmaQIMR Berghofer Medical Research Institute
(author)
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Törngren, ThereseLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Familjär bröstcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Familial Breast Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)onk-tsa
(author)
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Parsons, Michael T.QIMR Berghofer Medical Research Institute
(author)
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Pedersen, Inge S.Aalborg University,Aalborg University Hospital
(author)
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Teo, Soo H.University of Malaya,Cancer Research Initiatives Foundation
(author)
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Kruse, Torben A.Odense University Hospital
(author)
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Møller, PålNorwegian Radium Hospital
(author)
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Borg, ÅkeLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Familjär bröstcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Familial Breast Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)onk-abo
(author)
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Jensen, Uffe B.Aarhus University Hospital
(author)
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Christensen, Lise L.Aarhus University Hospital
(author)
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Singer, Christian F.Medical University of Vienna
(author)
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Muhr, DanielaMedical University of Vienna
(author)
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Santamarina, MartaBiomedical Network on Rare Diseases (CIBERER),Complejo Hospitalario Universitario de Santiago
(author)
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Brandao, RitaYukioka Hospital
(author)
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Andresen, Brage S.University of Southern Denmark
(author)
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Feng, Bing JianHuntsman Cancer Institute
(author)
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Canson, DaffodilQIMR Berghofer Medical Research Institute
(author)
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Richardson, Marcy E.Ambry Genetics Corporation
(author)
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Karam, RachidAmbry Genetics Corporation
(author)
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Pesaran, TinaAmbry Genetics Corporation
(author)
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LaDuca, HollyAmbry Genetics Corporation
(author)
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Conner, Blair R.Ambry Genetics Corporation
(author)
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Abualkheir, NellyAmbry Genetics Corporation
(author)
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Hoang, LilyAmbry Genetics Corporation
(author)
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Calléja, Fabienne M.G.R.Leiden University Medical Centre
(author)
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Andrews, Lesley
(author)
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James, Paul A.University of Melbourne,Peter MacCallum Cancer Centre
(author)
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Bunyan, DaveUniversity of Southampton
(author)
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Hamblett, Amanda
(author)
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Radice, PaoloIstituto Nazionale dei Tumori
(author)
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Goldgar, David E.Huntsman Cancer Institute
(author)
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Walker, Logan C.
(author)
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Engel, ChristophLeipzig University
(author)
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Claes, Kathleen B.M.Ghent University Hospital
(author)
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Macháčková, EvaMasaryk Memorial Cancer Institute
(author)
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Baralle, DianaUniversity of Southampton
(author)
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Viel, AlessandraCRO (Centro di Riferimento Oncologico) Aviano National Cancer Institute
(author)
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Wappenschmidt, BarbaraUniversity Hospital of Cologne
(author)
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Lazaro, ConxiCatalan Institute of Oncology
(author)
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Vega, AnaComplejo Hospitalario Universitario de Santiago,Biomedical Network on Rare Diseases (CIBERER)
(author)
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Vreeswijk, Maaike P.G.Leiden University Medical Centre
(author)
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de la Hoya, MiguelHospital Clinico San Carlos de Madrid
(author)
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Spurdle, Amanda B.QIMR Berghofer Medical Research Institute
(author)
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Odense University HospitalLeiden University Medical Centre
(creator_code:org_t)
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ENIGMA Consortium
Related titles
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In:Human Mutation: Hindawi Limited43:12, s. 1921-19441059-77941098-1004
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Thomassen, Mads
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Mesman, Romy L.S ...
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Hansen, Thomas V ...
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Menendez, Mireia
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Rossing, Maria
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Esteban-Sánchez, ...
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Tudini, Emma
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Törngren, Theres ...
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Parsons, Michael ...
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Pedersen, Inge S ...
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Teo, Soo H.
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Kruse, Torben A.
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Møller, Pål
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Borg, Åke
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Jensen, Uffe B.
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Christensen, Lis ...
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Singer, Christia ...
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Muhr, Daniela
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Santamarina, Mar ...
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Brandao, Rita
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Andresen, Brage ...
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Feng, Bing Jian
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Canson, Daffodil
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Richardson, Marc ...
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Karam, Rachid
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Pesaran, Tina
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LaDuca, Holly
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Conner, Blair R.
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Abualkheir, Nell ...
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Hoang, Lily
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Calléja, Fabienn ...
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Andrews, Lesley
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James, Paul A.
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Bunyan, Dave
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Hamblett, Amanda
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Radice, Paolo
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Goldgar, David E ...
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Walker, Logan C.
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Engel, Christoph
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Claes, Kathleen ...
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Macháčková, Eva
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Baralle, Diana
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Viel, Alessandra
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Wappenschmidt, B ...
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Lazaro, Conxi
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Vega, Ana
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Vreeswijk, Maaik ...
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de la Hoya, Migu ...
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Spurdle, Amanda ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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Human Mutation
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Lund University