Evidence map›Paper›PMID 37090572›Full record

ArticlebioRxiv : the preprint server for biology2023

DNA Repair Function Scores for 2172 Variants in the BRCA1 Amino-Terminus.

Mariame Diabate, Muhtadi M Islam, Gregory Nagy, Tapahsama Banerjee, Shruti Dhar, Nahum Smith, Aleksandra I Adamovich, Lea M Starita, Jeffrey D Parvin

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Mariame DiabateThe Ohio State University, Department of Biomedical Informatics, and The Ohio State University Comprehensive Center, Columbus, OH 43210.
Muhtadi M IslamThe Ohio State University, Department of Biomedical Informatics, and The Ohio State University Comprehensive Center, Columbus, OH 43210.
Gregory NagyThe Ohio State University, Department of Biomedical Informatics, and The Ohio State University Comprehensive Center, Columbus, OH 43210.
Tapahsama BanerjeeThe Ohio State University, Department of Biomedical Informatics, and The Ohio State University Comprehensive Center, Columbus, OH 43210.
Shruti DharThe Ohio State University, Department of Biomedical Informatics, and The Ohio State University Comprehensive Center, Columbus, OH 43210.
Nahum SmithThe University of Washington, Department of Genome Sciences, Seattle, WA 98195.
Aleksandra I AdamovichThe Ohio State University, Department of Biomedical Informatics, and The Ohio State University Comprehensive Center, Columbus, OH 43210.
Lea M StaritaThe University of Washington, Department of Genome Sciences, Seattle, WA 98195.
Jeffrey D ParvinThe Ohio State University, Department of Biomedical Informatics, and The Ohio State University Comprehensive Center, Columbus, OH 43210.
The Ohio State University · USUniversity of Washington · US

Funding

Multiplexed functional analysis of BRCA1and BARD1 missense variants in DNA repairR01CA228083 · NCI · OHIO STATE UNIVERSITY · PI PARVIN, JEFFREY D · 2019 to 2023
$2.4M
Integrative Training in Biomedical SystemsT32GM068412 · NIGMS · OHIO STATE UNIVERSITY · PI PARVIN, JEFFREY D · 2005 to 2020
$2.4M
NCI NIH HHS R01 CA228083NIGMS NIH HHS T32 GM068412
6 · The paper itself

Abstract

Single nucleotide variants are the most frequent type of sequence changes detected in the genome and these are frequently variants of uncertain significance (VUS). VUS are changes in DNA for which disease risk association is unknown. Thus, methods that classify the functional impact of a VUS can be used as evidence for variant interpretation. In the case of the breast and ovarian cancer specific tumor suppressor protein, BRCA1, pathogenic missense variants frequently score as loss of function in an assay for homology-directed repair (HDR) of DNA double-strand breaks. We previously published functional results using a multiplexed assay for 1056 amino acid substitutions residues 2-192 in the amino terminus of BRCA1. In this study, we have re-assessed the data from this multiplexed assay using an improved analysis pipeline. These new analysis methods yield functional scores for more variants in the first 192 amino acids of BRCA1, plus we report new results for BRCA1 amino acid residues 193-302. We now present the functional classification of 2172 BRCA1 variants in BRCA1 residues 2-302 using the multiplexed HDR assay. Comparison of the functional determinations of the missense variants with clinically known benign or pathogenic variants indicated 93% sensitivity and 100% specificity for this assay. The results from AUTHOR SUMMARY: Most missense substitutions in

Identifiers

PMID37090572
PMCPMC10120616
OpenAlexW4365148187

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.