23 research outputs found

    Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

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    The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification

    Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

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    Abstract The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.Peer reviewe

    2020 Dataset on local gambling regulations in Italy

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    The dataset provides the complete enumeration of gambling policies implemented by Italian Municipalities between 2003 and 2021. The dataset comprises information on all municipalities existing in 2017 and following years (thus considering also merging). The following variables are available: Municipality ISTAT Code (ID), Municipality Name (Name) Province, Region, Researcher, and a series of variables identifying the number and the type of rulings adopted (“regolamento”, “ordinanza” and “delibera”). The rulings are distinguished between identified and downloaded or only identified (because the document is no longer available). Additional variables describe municipal activism with other administrative acts (Anti-gambling Manifesto, events, projects or tax reductions). Overall, the dataset comprises 8031 units

    Reduced prevalence of fetal exposure to alcohol in Italy: a nationwide survey

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    Open data from the first and second observing runs of Advanced LIGO and Advanced Virgo

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    Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software

    Publisher’s Note: Observing gravitational-wave transient GW150914 with minimal assumptions [Phys. Rev. D 93, 122004 (2016)]

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    The gravitational-wave signal GW150914 was first identified on September 14, 2015, by searches forshort-duration gravitational-wave transients. These searches identify time-correlated transients in multipledetectors with minimal assumptions about the signal morphology, allowing them to be sensitive togravitational waves emitted by a wide range of sources including binary black hole mergers. Over theobservational period from September 12 to October 20, 2015, these transient searches were sensitive tobinary black hole mergers similar to GW150914 to an average distance of∌600Mpc. In this paper, wedescribe the analyses that first detected GW150914 as well as the parameter estimation and waveformreconstruction techniques that initially identified GW150914 as the merger of two black holes. We find thatthe reconstructed waveform is consistent with the signal from a binary black hole merger with a chirp massof∌30M⊙and a total mass before merger of∌70M⊙in the detector fram

    Search for intermediate mass black hole binaries in the first observing run of Advanced LIGO