| Title |
ClinGen’s RASopathy Expert Panel consensus methods for variant interpretation
|
|---|---|
| Published in |
Genetics in Medicine, March 2018
|
| DOI | 10.1038/gim.2018.3 |
| Pubmed ID | |
| Authors |
Bruce D Gelb, Hélène Cavé, Mitchell W Dillon, Karen W Gripp, Jennifer A Lee, Heather Mason-Suares, Katherine A Rauen, Bradley Williams, Martin Zenker, Lisa M Vincent, for the ClinGen RASopathy Working Group |
| Abstract |
PurposeStandardized and accurate variant assessment is essential for effective medical care. To that end, Clinical Genome (ClinGen) Resource clinical domain working groups (CDWGs) are systematically reviewing disease-associated genes for sufficient evidence to support disease causality and creating disease-specific specifications of American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) guidelines for consistent and accurate variant classification.MethodsThe ClinGen RASopathy CDWG established an expert panel to curate gene information and generate gene- and disease-specific specifications to ACMG-AMP variant classification framework. These specifications were tested by classifying 37 exemplar pathogenic variants plus an additional 66 variants in ClinVar distributed across nine RASopathy genes.ResultsRASopathy-related specifications were applied to 16 ACMG-AMP criteria, with 5 also having adjustable strength with availability of additional evidence. Another 5 criteria were deemed not applicable. Key adjustments to minor allele frequency thresholds, multiple de novo occurrence events and/or segregation, and strength adjustments impacted 60% of variant classifications. Unpublished case-level data from participating laboratories impacted 45% of classifications supporting the need for data sharing.ConclusionRAS-specific ACMG-AMP specifications optimized the utility of available clinical evidence and Ras/MAPK pathway-specific characteristics to consistently classify RASopathy-associated variants. These specifications highlight how grouping genes by shared features promotes rapid multigenic variant assessment without sacrificing specificity and accuracy.GENETICS in MEDICINE advance online publication, 1 March 2018; doi:10.1038/gim.2018.3. |
X Demographics
The data shown below were collected from the profiles of 40 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 11 | 28% |
| United Kingdom | 6 | 15% |
| Saudi Arabia | 1 | 3% |
| India | 1 | 3% |
| Bosnia and Herzegovina | 1 | 3% |
| Turkey | 1 | 3% |
| Cyprus | 1 | 3% |
| Taiwan | 1 | 3% |
| France | 1 | 3% |
| Other | 4 | 10% |
| Unknown | 12 | 30% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 20 | 50% |
| Scientists | 19 | 48% |
| Science communicators (journalists, bloggers, editors) | 1 | 3% |
Mendeley readers
The data shown below were compiled from readership statistics for 132 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 132 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 27 | 20% |
| Other | 25 | 19% |
| Student > Master | 12 | 9% |
| Student > Ph. D. Student | 10 | 8% |
| Student > Bachelor | 9 | 7% |
| Other | 14 | 11% |
| Unknown | 35 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 38 | 29% |
| Agricultural and Biological Sciences | 22 | 17% |
| Medicine and Dentistry | 21 | 16% |
| Neuroscience | 3 | 2% |
| Computer Science | 2 | 2% |
| Other | 6 | 5% |
| Unknown | 40 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 24. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 July 2019.
All research outputs
#1,572,938
of 25,394,764 outputs
Outputs from Genetics in Medicine
#522
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Outputs of similar age
#34,028
of 344,933 outputs
Outputs of similar age from Genetics in Medicine
#15
of 62 outputs
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