MétaCan
Menu
Back to cohort
Record W2788825237 · doi:10.1002/humu.23411

The <i>BRCA2</i> c.68-7T &gt; A variant is not pathogenic: A model for clinical calibration of spliceogenicity

2018· article· en· W2788825237 on OpenAlexaff
Mara Colombo, Irene López‐Perolio, Huong Meeks, Laura Caleca, Michael T. Parsons, Hongyan Li, Giovanna De Vecchi, Emma Tudini, Claudia Foglia, P Mondini, Siranoush Manoukian, Raquel Behar, E. Gómez, Marco Montagna, Dieter Niederacher, Ane Yde Schmidt, Liliana Varesco, Barbara Wappenschmidt, Manjeet K. Bolla, Joe Dennis, Kyriaki Michailidou, Qin Wang, Kristiina Aittomäki, Irene L. Andrulis, Hoda Anton‐Culver, Volker Arndt, Matthias W. Beckmann, Alicia Beeghly-Fadel, Javier Benı́tez, Bram Boeckx, Natalia Bogdanova, Stig E. Bojesen, Bernardo Bonanni, Hiltrud Brauch, Hermann Brenner, Barbara Burwinkel, Jenny Chang‐Claude, Don Conroy, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Peter Devilee, Thilo Dörk, Mikael Eriksson, Peter A. Fasching, Jonine D. Figueroa, Olivia Fletcher, Henrik Flyger, Marike Gabrielson, Montserrat García‐Closas, Graham G. Giles, Anna González‐Neira, Pascal Guénel, Christopher A. Haiman, Per Hall, Ute Hamann, Mikael Hartman, Jan Hauke, Antoinette Hollestelle, John L. Hopper, Anna Jakubowska, Audrey Jung, Veli‐Matti Kosma, Diether Lambrechts, Loid Le Marchand, Annika Lindblom, Jan Lubiński, Arto Mannermaa, Sara Margolin, Roger L. Milne, Susan L. Neuhausen, Heli Nevanlinna, Janet E. Olson, Paolo Peterlongo, Julian Peto, Katri Pylkäs, Elinor J. Sawyer, Marjanka K. Schmidt, Rita K. Schmutzler, Andreas Schneeweiß, Minouk J. Schoemaker, Mee‐Hoong See, Melissa C. Southey, Anthony J. Swerdlow, Soo‐Hwang Teo, Amanda E. Toland, Ian Tomlinson, Thérèse Truong, Christi J. van Asperen, Ans M.W. van den Ouweland, Lizet E. van der Kolk, Robert Winqvist, Drakoulis Yannoukakos, Wei Zheng, Alison M. Dunning, Douglas F. Easton, Alex Henderson, Frans B.L. Hogervorst, Louise Izatt, Kenneth Offitt, Lucy Side, Elizabeth J. van Rensburg, Study EMBRACE, Study HEBON, Lesley McGuffog, Antonis C. Antoniou, Georgia Chenevix‐Trench, Amanda B. Spurdle, Miguel de la Hoya, Paolo Radice

Bibliographic record

VenueHuman Mutation · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBRCA gene mutations in cancer
Canadian institutionsLunenfeld-Tanenbaum Research InstituteUniversity of Toronto
FundersCancer Council QueenslandCancer Research UKNational Health and Medical Research CouncilMedical Research CouncilInstituto de Salud Carlos IIIRigshospitaletAssociazione Italiana per la Ricerca sul CancroWellcome TrustNederlandse Organisatie voor Wetenschappelijk OnderzoekNational Cancer InstituteKWF KankerbestrijdingNational Institute for Health and Care ResearchTranscan
KeywordsBiologyOdds ratioGeneticsAlleleExonBreast cancerCancerGeneInternal medicineMedicine

Abstract

fetched live from OpenAlex

. There was neither evidence for increased risk of breast cancer (OR 1.03; 95% CI 0.86-1.24) nor for a deleterious effect of the variant when co-occurring with pathogenic variants. Our data provide for the first time robust evidence of the nonpathogenicity of the BRCA2 c.68-7T > A. Genetic and quantitative transcript analyses together inform the threshold for the ratio between functional and altered BRCA2 isoforms compatible with normal cell function. These findings might be exploited to assess the relevance for cancer risk of other BRCA2 spliceogenic variants.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.450
Threshold uncertainty score0.413

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.058
GPT teacher head0.366
Teacher spread0.308 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations20
Published2018
Admission routes1
Has abstractyes

Explore more

Same venueHuman MutationSame topicBRCA gene mutations in cancerFrench-language works237,207