Evidence map›Paper›PMID 41172994›Full record

ArticleAmerican journal of human genetics2025

BRCA1-, BRCA2-, and PALB2-related Fanconi anemia: Scope to expand disease phenotypic features and predict breast cancer risk in heterozygotes.

Sharon E Johnatty, Emma Tudini, Michael T Parsons, Kyriaki Michailidou, Maria Zanti, Daffodil M Canson, Aimee L Davidson, Tamar Berger, Rasim Ozgur Rosti, Christian P Kratz and 55 more

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Article in American journal of human genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

65 authors.

Sharon E JohnattyPopulation Health Program, QIMR Berghofer, Brisbane, QLD, Australia.
Emma TudiniPopulation Health Program, QIMR Berghofer, Brisbane, QLD, Australia.
Michael T ParsonsPopulation Health Program, QIMR Berghofer, Brisbane, QLD, Australia.
Kyriaki MichailidouBiostatistics Unit, the Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus.
Maria ZantiBiostatistics Unit, the Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus.
Daffodil M CansonPopulation Health Program, QIMR Berghofer, Brisbane, QLD, Australia.
Aimee L DavidsonPopulation Health Program, QIMR Berghofer, Brisbane, QLD, Australia.
Tamar BergerLaboratory of Genome Maintenance, the Rockefeller University, New York, NY, USA.
Rasim Ozgur RostiLaboratory of Genome Maintenance, the Rockefeller University, New York, NY, USA.
Christian P KratzPediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Reinhard KalbDepartment of Human Genetics, University of Würzburg, Biocenter, Würzburg, Germany.
Lisa J McReynoldsClinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Neelam GiriClinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Marcy E RichardsonAmbry Genetics, Aliso Viejo, CA, USA.
Tina PesaranAmbry Genetics, Aliso Viejo, CA, USA.
Jordi SurrallésInstitut de Recerca Sant Pau (IR Sant Pau), Universitat Autònoma de Barcelona, and CIBERER, Barcelona, Spain.
Roser PujolInstitut de Recerca Sant Pau (IR Sant Pau), Universitat Autònoma de Barcelona, and CIBERER, Barcelona, Spain.
Babu Rao VundintiICMR-National Institute of Immunohaematology, Mumbai, India.
Merin GeorgeICMR-National Institute of Immunohaematology, Mumbai, India.
Kara N MaxwellDivision of Hematology/Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Kate NathansonAbramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Susan DomchekDivision of Hematology/Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Moisés Ó Fiesco-RoaLaboratorio de Citogenética, Instituto Nacional de Pediatría (INP), Mexico City, Mexico; Programa de Maestría y Doctorado en Ciencias Médicas, Odontológicas y de la Salud, UNAM, Mexico City, Mexico.
Sara FriasLaboratorio de Citogenética, Instituto Nacional de Pediatría (INP), Mexico City, Mexico; Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, UNAM, Mexico City, Mexico.
Benilde García-de-TeresaLaboratorio de Citogenética, Instituto Nacional de Pediatría (INP), Mexico City, Mexico.
Marjolijn JongmansPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Seema LalaniDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Merel MaiburgDepartment of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
Katrina PrescottYorkshire Regional Genetics Service, Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital, Leeds, UK.
Rachel RobinsonYorkshire Regional Genetics Service, Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital, Leeds, UK.
Sulekha RajagopalanDepartment of Clinical Genetics, Liverpool Hospital, Sydney, NSW, Australia.
Lot Snijders BlokHuman Genetics Department, Radboud University Medical Center, Nijmegen, the Netherlands.
Suzanna E L TempleDepartment of Clinical Genetics, Liverpool Hospital, Sydney, NSW, Australia; School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.
Kathy TuckerHereditary Cancer Centre, Prince of Wales Hospital, Randwick, NSW, Australia; Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW, Australia.
Arleen D AuerbachHuman Genetics and Hematology Program, the Rockefeller University, New York, NY, USA.
Maria I CancioDepartment of Pediatrics, Stem Cell Transplantation and Cellular Therapies Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jennifer A KennedyDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Margaret L MacMillanDivision of Pediatric Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
Rebecca TryonDivision of Pediatric Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA; Department of Genetics, M Health Fairview, Minneapolis, MN, USA.
John E WagnerDivision of Pediatric Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
Michael WalshDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nicholas J BoddickerDepartment of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic, Rochester, MN, USA.
Chunling HuDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Jeffrey N WeitzelUniversity of Kansas Cancer Center, Kansas City, KS, USA.
Alexander J M DingemansHuman Genetics Department, Radboud University Medical Center, Nijmegen, the Netherlands.
Johanna HadlerPopulation Health Program, QIMR Berghofer, Brisbane, QLD, Australia.
Nitsan RotenbergPopulation Health Program, QIMR Berghofer, Brisbane, QLD, Australia.
Lobna Ramadane-MorchadiMolecular Oncology Laboratory, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain.
Miguel de la HoyaMolecular Oncology Laboratory, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain.
Paul JamesSir Peter MacCallum Department of Oncology, the University of Melbourne, Melbourne, VIC, Australia.
Thomas Van Overeem HansenDepartment of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Maaike P G VreeswijkDepartment of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Logan C WalkerDepartment of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.
Shyam K SharanMouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
Douglas F EastonDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK; Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
Fergus CouchDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Agata SmogorzewskaLaboratory of Genome Maintenance, the Rockefeller University, New York, NY, USA.
Adam NelsonSchool of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia; Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW, Australia.
Joanne NgeowPopulation and Global Health, Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Singapore; Cancer Genetics Service, National Cancer Center, Singapore, Singapore.
Marc TischkowitzDepartment of Genomic Medicine, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Encarnacion Gomez-GarciaMaastricht University, Maastricht, the Netherlands.
CARRIERS ConsortiumDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Breast Cancer Association ConsortiumDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
ENIGMA ConsortiumPopulation Health Program, QIMR Berghofer, Brisbane, QLD, Australia.
Amanda B SpurdlePopulation Health Program, QIMR Berghofer, Brisbane, QLD, Australia; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia. Electronic address: amanda.spurdle@qimrb.edu.au.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Curation Expert Panels for BRCA1/2 and Hereditary Breast, Ovarian and Pancreatic (HBOP) Cancer GenesU24CA258058 · NCI · MAYO CLINIC ROCHESTER · PI Fergus Joseph Couch · 2022 to 2026
$1.3M
NCI NIH HHS P30 CA008748NCI NIH HHS U24 CA258058
6 · The paper itself

Abstract

The recessive Fanconi anemia (FA) phenotype is used to classify BRCA1 (FANCS), BRCA2 (FANCD1), and PALB2 (FANCN) variants with respect to dominant hereditary breast-ovarian cancer syndrome. We assessed its utility by examining the phenotypic spectrum observed in individuals with bi-allelic BRCA1, BRCA2, or PALB2 pathogenic variants and exploring the relationship between cancer presentation and allele severity score based on variant molecular features. A data collection instrument comprising 158 Human Phenotype Ontology (HPO) terms was used to document clinical features for individuals with FA from published and/or prospectively collected sources (total n = 172, 43 previously unpublished). Distinct FA-related variants (15 BRCA1, 123 BRCA2, and 22 PALB2) were annotated for predicted molecular impact, location, observed splicing or functional impact, and potential in-frame splicing rescue and used to assign different permutations of allele severity scores, which were assessed for correlation with FA presentation features. The association of BRCA1 and BRCA2 allele severity score with the magnitude of breast cancer risk in heterozygotes was evaluated using case-control analysis. Clinical features extended beyond the HPO list, including 84 terms related by hierarchy and 94 additional terms. The BRCA2 genotype severity score was associated with age at cancer diagnosis in individuals with FA (p = 1.8 × 10

Indexed as

BRCA1 ProteinBRCA2 ProteinBreast NeoplasmsFanconi AnemiaFanconi Anemia Complementation Group N ProteinAdultAllelesCase-Control StudiesFemaleGenetic Predisposition to DiseaseHereditary Breast and Ovarian Cancer SyndromeHeterozygoteHumansPhenotypeBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanFanconi Anemia Complementation Group N ProteinPALB2 protein, humanACMGBRCA1BRCA2breast cancer riskFanconi anemiagenetic variant classificationHuman Phenotype OntologyPALB2pathogenicity

Identifiers

PMID41172994
PMCPMC12626413

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.