Clinical, splicing and functional analysis to classify BRCA2 exon 3 variants: application of a points-based ACMG/AMP approach

Accepted/In Press date: 11 August 2022

e-pub ahead of print date: 23 October 2022

Published date: December 2022

Additional Information: Funding Information: The authors thank J. Jonkers and P. Bouwman (Netherlands Cancer Institute, Amsterdam, the Netherlands) for the I‐Sce1‐mCherry plasmid; S.K. Sharan (National Cancer Institute at Frederick, Frederick, USA) for the Pl2F7 conditional Brca2 knockout mES cell line (PMID: 18607349); M. Jasin (Memorial Sloan‐Kettering Cancer Center, New York, USA) for the DR‐GFP reporter plasmid (PMID: 11239455). The authors wish also to thank all the members of the ICO Hereditary Cancer Program. LCW was supported by the Royal Society of New Zealand Rutherford Discovery Fellowship. The FPGMX thanks members of the Cancer Genetics group (IDIS): Miguel Aguado, Olivia Fuentes, and Ana Crujeiras. The work of MPGV was financially supported by the Dutch Cancer Society KWF (UL2012‐5649 and Pink Ribbon‐11704). The work by PM was supported by a “Pink Ribbon” grant #194751 from Den Norske Kreftforening to E.H. The work of MdlH was supported by Spanish Instituto de Salud Carlos III (ISCIII) funding grant PI 20/00110, an initiative of the Spanish Ministry of Economy and Innovation. ABS, MTP and ET were supported by NHMRC Funding (APP177524, APP1104808). The work by CL and MM received institutional support by CERCA Program/Generalitat de Catalunya and grant support by the Carlos III National Health Institute funded by FEDER funds—a way to build Europe—[PI19/00553; PI16/00563; SAF2015‐68016‐R and CIBERONC]; the Government of Catalonia [Pla estratègic de recerca i innovació en salut (PERIS_MedPerCan and URDCat projects), 2017SGR1282 and 2017SGR496]. The Baralle lab is supported by NIHR Research Professorship to DB (RP‐2016‐07‐011). The work of AV was supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III (ISCIII) through Research Activity Intensification Program (contract grant numbers: INT15/00070, INT16/00154, INT17/00133, and INT20/00071), and through Centro de Investigación Biomédica en Red de Enfermedades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018); Autonomous Government of Galicia (Consolidation and structuring program: IN607B), and by the Fundación Mutua Madrileña (call 2018). The German Consortium of Hereditary Breast and Ovarian Cancer (GC‐HBOC) is supported by the German Cancer Aid (Grant nos. 110837 and 70114178), (RKS) and by the Federal Ministry of Education and Research (Grant no. 01GY1901), (RKS). The work of EMA was supported by the Ministry of Health of the Czech Republic MH CZ—DRO (MMCI, 00209805) and AZV project NU20‐03‐00285. Institutional support by Italian Ministy of Health, Ricerca Corrente of CRO Aviano, Line 1 (AVI). Funding Information: The authors thank J. Jonkers and P. Bouwman (Netherlands Cancer Institute, Amsterdam, the Netherlands) for the I-Sce1-mCherry plasmid; S.K. Sharan (National Cancer Institute at Frederick, Frederick, USA) for the Pl2F7 conditional Brca2 knockout mES cell line (PMID: 18607349); M. Jasin (Memorial Sloan-Kettering Cancer Center, New York, USA) for the DR-GFP reporter plasmid (PMID: 11239455). The authors wish also to thank all the members of the ICO Hereditary Cancer Program. LCW was supported by the Royal Society of New Zealand Rutherford Discovery Fellowship. The FPGMX thanks members of the Cancer Genetics group (IDIS): Miguel Aguado, Olivia Fuentes, and Ana Crujeiras. The work of MPGV was financially supported by the Dutch Cancer Society KWF (UL2012-5649 and Pink Ribbon-11704). The work by PM was supported by a “Pink Ribbon” grant #194751 from Den Norske Kreftforening to E.H. The work of MdlH was supported by Spanish Instituto de Salud Carlos III (ISCIII) funding grant PI 20/00110, an initiative of the Spanish Ministry of Economy and Innovation. ABS, MTP and ET were supported by NHMRC Funding (APP177524, APP1104808). The work by CL and MM received institutional support by CERCA Program/Generalitat de Catalunya and grant support by the Carlos III National Health Institute funded by FEDER funds—a way to build Europe—[PI19/00553; PI16/00563; SAF2015-68016-R and CIBERONC]; the Government of Catalonia [Pla estratègic de recerca i innovació en salut (PERIS_MedPerCan and URDCat projects), 2017SGR1282 and 2017SGR496]. The Baralle lab is supported by NIHR Research Professorship to DB (RP-2016-07-011). The work of AV was supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III (ISCIII) through Research Activity Intensification Program (contract grant numbers: INT15/00070, INT16/00154, INT17/00133, and INT20/00071), and through Centro de Investigación Biomédica en Red de Enfermedades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018); Autonomous Government of Galicia (Consolidation and structuring program: IN607B), and by the Fundación Mutua Madrileña (call 2018). The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (Grant nos. 110837 and 70114178), (RKS) and by the Federal Ministry of Education and Research (Grant no. 01GY1901), (RKS). The work of EMA was supported by the Ministry of Health of the Czech Republic MH CZ—DRO (MMCI, 00209805) and AZV project NU20-03-00285. Institutional support by Italian Ministy of Health, Ricerca Corrente of CRO Aviano, Line 1 (AVI). Publisher Copyright: © 2022 The Authors. Human Mutation published by Wiley Periodicals LLC.

Keywords: ACMG/AMP classification, BRCA2, dPCR, functional analysis, quantitation, splicing

Local EPrints ID: 469460

URI: http://eprints.soton.ac.uk/id/eprint/469460

DOI: doi:10.1002/humu.24449

ISSN: 1059-7794

PURE UUID: 3a4071c8-850a-4e63-af93-d5d7e3f27a5a

ORCID for Diana Baralle: orcid.org/0000-0003-3217-4833

Date deposited: 15 Sep 2022 16:31

Last modified: 17 Mar 2024 07:27