-
Je něco špatně v tomto záznamu ?
Clinical, splicing, and functional analysis to classify BRCA2 exon 3 variants: Application of a points-based ACMG/AMP approach
M. Thomassen, RLS. Mesman, TVO. Hansen, M. Menendez, M. Rossing, A. Esteban-Sánchez, E. Tudini, T. Törngren, MT. Parsons, IS. Pedersen, SH. Teo, TA. Kruse, P. Møller, Å. Borg, UB. Jensen, LL. Christensen, CF. Singer, D. Muhr, M. Santamarina, R....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
PubMed
35979650
DOI
10.1002/humu.24449
Knihovny.cz E-zdroje
- MeSH
- alternativní sestřih MeSH
- geny BRCA2 * MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- místa sestřihu RNA * MeSH
- myši MeSH
- protein BRCA2 genetika metabolismus MeSH
- sestřih RNA MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
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.
Ambry Genetics Aliso Viejo California USA
Breast Cancer Research Programme Cancer Research Malaysia Subang Jaya Selangor Malaysia
Center for Genomic Medicine Rigshospitalet Copenhagen University Hospital Copenhagen Denmark
Centre for Medical Genetics Ghent University Gent Belgium
Centro de Investigación en Red de Enfermedades Raras Madrid Spain
Clinical Cancer Research Center Aalborg University Hospital Aalborg Denmark
Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Clinical Genetics Aarhus University Hospital Aarhus N Denmark
Department of Clinical Genetics Maastricht University Medical Center Maastricht the Netherlands
Department of Clinical Genetics Odense University Hospital Odence C Denmark
Department of Clinical Genetics Rigshospitalet Copenhagen University Hospital Copenhagen Denmark
Department of Clinical Medicine Aalborg University Aalborg Denmark
Department of Human Genetics Leiden University Medical Center Leiden the Netherlands
Department of Molecular Medicine Aarhus University Hospital Aarhus Denmark
Department of OB GYN and Comprehensive Cancer Center Medical University of Vienna Vienna Austria
Department of Pathology and Biomedical Science University of Otago Christchurch New Zealand
Department of Surgery Faculty of Medicine University of Malaya Kuala Lumpur Malaysia
Department of Tumour Biology The Norwegian Radium Hospital Oslo University Hospital Oslo Norway
Division of Oncology Department of Clinical Sciences Lund Lund University Lund Sweden
Fundación Pública Galega de Medicina Xenómica Santiago de Compostela Spain
Hereditary Cancer Clinic Nelune Comprehensive Cancer Care Centre Sydney New South Wales Australia
Human Development and Health Faculty of Medicine University of Southampton Southampton UK
Institute for Medical Informatics Statistics and Epidemiology University of Leipzig Leipzig Germany
Middlesex Health Shoreline Cancer Center Westbrook Connecticut USA
Molecular Diagnostics Aalborg University Hospital Aalborg Denmark
Molecular Oncology Laboratory CIBERONC Hospital Clinico San Carlos IdISSC Madrid Spain
Parkville Familial Cancer Centre Peter MacCallum Cancer Center Melbourne Victoria Australia
Sir Peter MacCallum Department of Oncology The University of Melbourne Melbourne Victoria Australia
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc22032466
- 003
- CZ-PrNML
- 005
- 20230131150700.0
- 007
- ta
- 008
- 230120s2022 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1002/humu.24449 $2 doi
- 035 __
- $a (PubMed)35979650
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Thomassen, Mads $u Department of Clinical Genetics, Odense University Hospital, Odence C, Denmark $1 https://orcid.org/0000000300781217
- 245 10
- $a Clinical, splicing, and functional analysis to classify BRCA2 exon 3 variants: Application of a points-based ACMG/AMP approach / $c M. Thomassen, RLS. Mesman, TVO. Hansen, M. Menendez, M. Rossing, A. Esteban-Sánchez, E. Tudini, T. Törngren, MT. Parsons, IS. Pedersen, SH. Teo, TA. Kruse, P. Møller, Å. Borg, UB. Jensen, LL. Christensen, CF. Singer, D. Muhr, M. Santamarina, R. Brandao, BS. Andresen, BJ. Feng, D. Canson, ME. Richardson, R. Karam, T. Pesaran, H. LaDuca, BR. Conner, N. Abualkheir, L. Hoang, FMGR. Calléja, L. Andrews, PA. James, D. Bunyan, A. Hamblett, P. Radice, DE. Goldgar, LC. Walker, C. Engel, KBM. Claes, E. Macháčková, D. Baralle, A. Viel, B. Wappenschmidt, C. Lazaro, A. Vega, ENIGMA Consortium, MPG. Vreeswijk, M. de la Hoya, AB. Spurdle
- 520 9_
- $a 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.
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a myši $7 D051379
- 650 _2
- $a alternativní sestřih $7 D017398
- 650 _2
- $a protein BRCA2 $x genetika $x metabolismus $7 D024682
- 650 12
- $a geny BRCA2 $7 D024522
- 650 12
- $a místa sestřihu RNA $7 D022821
- 650 _2
- $a sestřih RNA $7 D012326
- 650 _2
- $a messenger RNA $x genetika $x metabolismus $7 D012333
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Mesman, Romy L S $u Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands $1 https://orcid.org/0000000197837138
- 700 1_
- $a Hansen, Thomas V O $u Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- 700 1_
- $a Menendez, Mireia $u Hereditary Cancer Program, Catalan Institute of Oncology, ONCOBELL-IDIBELL-IDTP, CIBERONC, Hospitalet de Llobregat, Spain
- 700 1_
- $a Rossing, Maria $u Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- 700 1_
- $a Esteban-Sánchez, Ada $u Molecular Oncology Laboratory, CIBERONC, Hospital Clinico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Madrid, Spain
- 700 1_
- $a Tudini, Emma $u Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia $1 https://orcid.org/0000000258347862
- 700 1_
- $a Törngren, Therese $u Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
- 700 1_
- $a Parsons, Michael T $u Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia $1 https://orcid.org/0000000332428477
- 700 1_
- $a Pedersen, Inge S $u Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark $u Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark $u Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- 700 1_
- $a Teo, Soo H $u Breast Cancer Research Programme, Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia $u Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
- 700 1_
- $a Kruse, Torben A $u Department of Clinical Genetics, Odense University Hospital, Odence C, Denmark
- 700 1_
- $a Møller, Pål $u Department of Tumour Biology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
- 700 1_
- $a Borg, Åke $u Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
- 700 1_
- $a Jensen, Uffe B $u Department of Clinical Genetics, Aarhus University Hospital, Aarhus N, Denmark
- 700 1_
- $a Christensen, Lise L $u Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
- 700 1_
- $a Singer, Christian F $u Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
- 700 1_
- $a Muhr, Daniela $u Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
- 700 1_
- $a Santamarina, Marta $u Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain $u Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain $u Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain
- 700 1_
- $a Brandao, Rita $u Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands
- 700 1_
- $a Andresen, Brage S $u Department of Biochemistry and Molecular Biology and the Villum Center for Bioanalytical Sciences, University of Southern Denmark, Odense, Denmark $1 https://orcid.org/0000000174883035
- 700 1_
- $a Feng, Bing-Jian $u Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, USA
- 700 1_
- $a Canson, Daffodil $u Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
- 700 1_
- $a Richardson, Marcy E $u Ambry Genetics, Aliso Viejo, California, USA
- 700 1_
- $a Karam, Rachid $u Ambry Genetics, Aliso Viejo, California, USA $1 https://orcid.org/000000025645498X
- 700 1_
- $a Pesaran, Tina $u Ambry Genetics, Aliso Viejo, California, USA
- 700 1_
- $a LaDuca, Holly $u Ambry Genetics, Aliso Viejo, California, USA
- 700 1_
- $a Conner, Blair R $u Ambry Genetics, Aliso Viejo, California, USA
- 700 1_
- $a Abualkheir, Nelly $u Ambry Genetics, Aliso Viejo, California, USA
- 700 1_
- $a Hoang, Lily $u Ambry Genetics, Aliso Viejo, California, USA
- 700 1_
- $a Calléja, Fabienne M G R $u Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands
- 700 1_
- $a Andrews, Lesley $u Hereditary Cancer Clinic, Nelune Comprehensive Cancer Care Centre, Sydney, New South Wales, Australia
- 700 1_
- $a James, Paul A $u Parkville Familial Cancer Centre, Peter MacCallum Cancer Center, Melbourne, Victoria, Australia $u Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia $1 https://orcid.org/0000000243614657
- 700 1_
- $a Bunyan, Dave $u Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
- 700 1_
- $a Hamblett, Amanda $u Middlesex Health Shoreline Cancer Center, Westbrook, Connecticut, USA
- 700 1_
- $a Radice, Paolo $u Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy
- 700 1_
- $a Goldgar, David E $u Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, USA $1 https://orcid.org/0000000306979347
- 700 1_
- $a Walker, Logan C $u Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand $1 https://orcid.org/0000000300183719
- 700 1_
- $a Engel, Christoph $u Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
- 700 1_
- $a Claes, Kathleen B M $u Centre for Medical Genetics, Ghent University, Gent, Belgium $1 https://orcid.org/0000000308417372
- 700 1_
- $a Macháčková, Eva $u Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic
- 700 1_
- $a Baralle, Diana $u Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK $1 https://orcid.org/0000000235606980
- 700 1_
- $a Viel, Alessandra $u Division of Functional Onco-genomics and Genetics, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy
- 700 1_
- $a Wappenschmidt, Barbara $u Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany $u Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- 700 1_
- $a Lazaro, Conxi $u Hereditary Cancer Program, Catalan Institute of Oncology, ONCOBELL-IDIBELL-IDTP, CIBERONC, Hospitalet de Llobregat, Spain
- 700 1_
- $a Vega, Ana $u Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain $u Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain $u Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain $1 https://orcid.org/0000000274165137
- 700 1_
- $a Vreeswijk, Maaike P G $u Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands $1 https://orcid.org/0000000340689271
- 700 1_
- $a de la Hoya, Miguel $u Molecular Oncology Laboratory, CIBERONC, Hospital Clinico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Madrid, Spain $1 https://orcid.org/0000000281131410
- 700 1_
- $a Spurdle, Amanda B $u Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia $1 https://orcid.org/0000000313377897
- 710 2_
- $a ENIGMA Consortium
- 773 0_
- $w MED00002078 $t Human mutation $x 1098-1004 $g Roč. 43, č. 12 (2022), s. 1921-1944
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/35979650 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y p $z 0
- 990 __
- $a 20230120 $b ABA008
- 991 __
- $a 20230131150656 $b ABA008
- 999 __
- $a ok $b bmc $g 1891306 $s 1183801
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2022 $b 43 $c 12 $d 1921-1944 $e 20221023 $i 1098-1004 $m Human mutation $n Hum Mutat $x MED00002078
- LZP __
- $a Pubmed-20230120
