71e02fc571b87f50f6d984f0cbc4954595f651c1 abenetpa Mon Aug 3 17:08:52 2020 -0700 finished description page ClinGen composite ref #24818 diff --git src/hg/makeDb/trackDb/human/clinGen.html src/hg/makeDb/trackDb/human/clinGen.html index 7ce2f1f..57ee5dc 100644 --- src/hg/makeDb/trackDb/human/clinGen.html +++ src/hg/makeDb/trackDb/human/clinGen.html @@ -1,124 +1,171 @@ <H2>Description</H2> <p> <div class="warn-note" style="border: 2px solid #9e5900; padding: 5px 20px; background-color: #ffe9cc;"> <p><span style="font-weight: bold; color: #c70000;">NOTE:</span><br> <b>These data are for research purposes only. While the ClinGen data are open to the public, users seeking information about a personal medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal medical questions. </p> <p> UCSC presents these data for use by qualified professionals, and even such professionals should use caution in interpreting the significance of information found here. No single data point should be taken at face value and such data should always be used in conjunction with as much corroborating data as possible. No treatment protocols should be developed or patient advice given on the basis of these data without careful consideration of all possible sources of information. </p> <p> No attempt to identify individual patients should be undertaken. No one is authorized to attempt to identify patients by any means. </p> </b> </div> <p> The <a target="_blank" href="https://clinicalgenome.org"><b>Clinical Genome Resource (ClinGen)</b></a> tracks display data generated from several key curation activities related to <a target="_blank" href="https://clinicalgenome.org/curation-activities/gene-disease-validity/"><b>gene-disease validity</b></a>, <a target="_blank" href="https://clinicalgenome.org/curation-activities/dosage-sensitivity/" ><b>dosage sensitivity</b></a>, and <a target="_blank" href="https://clinicalgenome.org/curation-activities/variant-pathogenicity/"><b>variant pathogenicity</b></a>. ClinGen is a <a target="_blank" href="https://www.nih.gov/">National Institute of Health (NIH)</a>-funded program dedicated to building a central resource that defines the clinical relevance of genes and variants for use in precision medicine and research. This is accomplished by harnessing the data from both research efforts and clinical genetic testing and using it to propel expert and machine-driven curation activities. ClinGen works closely with the <a target="_blank" href="https://www.nlm.nih.gov/">National Center for Biotechnology Information (NCBI)</a> of the <a target="_blank" href="https://www.nlm.nih.gov/">National Library of Medicine (NLM)</a> which distributes part of this information through its <a target="_blank" href="https://www.ncbi.nlm.nih.gov/clinvar/">ClinVar</a> database. </p> <p> The available data tracks are: <ul> <li><b>Clinical Genome Resource Structural Variants (ClinGen Structural Variants)</b> - Shows curated copy number variants (CNVs) with sufficient pathogenic or benign evidence as a mechanism for disease from the dbVar study <a target="_blank" href="https://www.ncbi.nlm.nih.gov/dbvar/studies/nstd45/">nstd45</a> (ClinGen Curated Dosage Sensitivity Map-obsoleted). </li> -<li><b>Clinical Genome Resource Dosage Sensitivity (ClinGen Dosage Sensitivity)</b> - +<li><b>Clinical Genome Resource Dosage Sensitivity Map Haploinsufficiency (ClinGen Haploinsufficiency) and -Triplosensitivity (ClinGen Triplosensitivity)</b> - Shows evidence supporting or refuting haploinsufficiency (loss) and triplosensitivity (gain) as mechanisms for disease at gene-level and larger genomic regions. </li> </ul> </p> - +<p> +A <b>rating system</b> is used to classify the <b>evidence</b> supporting or refuting dosage + sensitivity for individual genes and regions, which takes in consideration the following criteria: +number of causative mutations reported, patterns of inheritance, consistency of phenotype, evidence +from large-scale case-control studies, mutational mechanisms, data from public genome variation +databases, and expert consensus opinion. +</p> +<p> +The system is intended to be of a "dynamic nature", with regions being reevaluated periodically to +incorporate emerging evidence. The evidence collected is displayed within a publicly available +<a target="_blank" href="https://search.clinicalgenome.org/kb/gene-dosage">database</a>. +Evidence that haploinsufficiency or triplosensitivity of a gene is associated with a specific +phenotype will aid in the interpretive assessment of CNVs including that gene. +</p> <h2>Display Conventions</h2> <p> +<b>Structural Variants</b> are shaded according to variant type, +<b><font color="red">red</font color></b> for CNV loss, <b><font color="blue"> blue</font color></b> +for CNV gain. +<p> +Mouseover on items indicates affected protein-coding genes, size of the variant, variant type, and +associated phenotype. When more than 2 genes are affected by a variant, the full +list can be obtained by clicking on the item and reading the details page. +</p> +<p> +All tracks can be filtered according to the size of the variant, variant type (loss or gain), and +clinical significance (benign or pathogenic). +</p> +<p> +<b>Dosage Scores</b> are used to classify the evidence of the supporting dosage sensitivity map: +<dl> +<dd><b>0</b> - no evidence available</dd> +<dd><b>1</b> - little evidence for dosage pathogenicity</dd> +<dd><b>2</b> - some evidence for dosage pathogenicity</dd> +<dd><b>3</b> - sufficient evidence for dosage pathogenicity</dd> +<dd><b>30</b> - gene associated with autosomal recessive phenotype</dd> +<dd><b>40</b> - dosage sensitivity unlikely</dd> +</dl> +</p> +For more information on the use of the scores see the ClinGen +<a target="_blank" href="https://clinicalgenome.org/tools/cnv-webinar/faq/">FAQs</a>. +Items are shaded according to dosage sensitivity type. <b><font color="red">red</font></b> for haploinsufficiency, +<b><font color="blue">blue</font></b> for triplosensitivity, +and <B><font color="#a8a8a8">grey</font></b> for other evidence scores or +for genes/regions that have not been evaluated yet or no evidence is available. A light to dark +gradient color is used according to the degree of supporting evidence. +</p> +<p> +Mouseover on items shows the supporting evidence of dosage sensitivity and respective scores. All +tracks can be filtered according to the supporting evidence of dosage sensitivity. +</p> +<p> These tracks are multi-view composite tracks that contain multiple data types (views). Each view within a track has separate display controls, as described -<a href="../goldenPath/help/multiView.html">here</a>. Some ClinGen tracks contain multiple -subtracks, corresponding to subsets of data. The user can select which subtracks are displayed via -the display controls on the track details page. +<a href="../goldenPath/help/multiView.html">here</a>. </p> <h2>Data Access</h2> <p> The raw data can be explored interactively with the <a href="../cgi-bin/hgTables">Table Browser</a>, or the <a href="../cgi-bin/hgIntegrator">Data Integrator</a>. For automated analysis, the data may be queried from our REST API. Please refer to our <a href="https://groups.google.com/a/soe.ucsc.edu/forum/#!forum/genome">mailing list archives</a> for questions, or our <a href="../FAQ/FAQdownloads.html#downloads36">Data Access FAQ</a> for more information. </p> <h2>Credits</h2> <p> Thank you to ClinGen and NCBI, especially Erin Rooney Riggs for technical coordination and consultation, and to Christopher Lee, Anna Benet-Pages, and Maximilian Haeussler of the Genome Browser team for engineering the track display. </p> <h2>References</h2> <p> Rehm HL, Berg JS, Brooks LD, Bustamante CD, Evans JP, Landrum MJ, Ledbetter DH, Maglott DR, Martin CL, Nussbaum RL <em>et al</em>. <a href="https://www.ncbi.nlm.nih.gov/pubmed/26014595" target="_blank"> ClinGen--the Clinical Genome Resource</a>. <em>N Engl J Med</em>. 2015 Jun 4;372(23):2235-42. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/26014595" target="_blank">26014595</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4474187/" target="_blank">PMC4474187</a> </p> <p> Riggs ER, Church DM, Hanson K, Horner VL, Kaminsky EB, Kuhn RM, Wain KE, Williams ES, Aradhya S, Kearney HM <em>et al</em>. <a href="https://www.ncbi.nlm.nih.gov/pubmed/22097934" target="_blank"> Towards an evidence-based process for the clinical interpretation of copy number variation</a>. <em>Clin Genet</em>. 2012 May;81(5):403-12. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/22097934" target="_blank">22097934</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008023/" target="_blank">PMC5008023</a> </p> <p> Strande NT, Riggs ER, Buchanan AH, Ceyhan-Birsoy O, DiStefano M, Dwight SS, Goldstein J, Ghosh R, Seifert BA, Sneddon TP <em>et al</em>. <a href="https://www.ncbi.nlm.nih.gov/pubmed/28552198" target="_blank"> Evaluating the Clinical Validity of Gene-Disease Associations: An Evidence-Based Framework Developed by the Clinical Genome Resource</a>. <em>Am J Hum Genet</em>. 2017 Jun 1;100(6):895-906. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/28552198" target="_blank">28552198</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473734/" target="_blank">PMC5473734</a> </p>