11bc662f36e84395bdfb111d4bc655ea51d02f8a lrnassar Wed Oct 16 12:56:47 2024 -0700 Ordering the references, feedback from CR. Refs #34624 diff --git src/hg/makeDb/trackDb/human/clinGen.html src/hg/makeDb/trackDb/human/clinGen.html index c32a418..45d8e29 100644 --- src/hg/makeDb/trackDb/human/clinGen.html +++ src/hg/makeDb/trackDb/human/clinGen.html @@ -1,265 +1,266 @@ <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 initiative dedicated to identifying clinically relevant 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>ClinGen 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> <li><b>ClinGen Gene-Disease Validity Classification (ClinGen Validity)</b> - Provides a semi-qualitative measurement for the strength of evidence of a gene-disease relationship. </li> <li><b>Clingen CSPEC variant interpretation VCEP specifications</b> - Identifies loci that have <a target="_blank" href="https://cspec.genome.network/cspec/ui/svi/">ClinGen criteria Specification (CSpec)</a> information. This is used and applied by ClinGen Variant Curation Expert Panels (VCEPs) and biocurators in the classification of variants. </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 variants 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://dosage.clinicalgenome.org/index.shtml">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 or genomic region. </p> <p> Similarly, a <b>qualitative classification system</b> is used to correlate the <b>evidence</b> of a gene-disease relationship: "Definitive", "Strong", "Moderate", "Limited", "Animal Model Only", "No Known Disease Relationship", "Disputed", or "Refuted". </p> <h2>Display Conventions</h2> <h3>Haploinsufficiency/Triplosensitivity tracks</h3> <p> Items are shaded according to dosage sensitivity type, <b><font color="red">red</font></b> for haploinsufficiency score 3, <b><font color="blue">blue</font></b> for triplosensitivity score 3, and <B><font color="#a8a8a8">grey</font></b> for other evidence scores or not yet evaluated). Mouseover on items shows the supporting evidence of dosage sensitivity. Tracks can be filtered according to the supporting evidence of dosage sensitivity. <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> <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>. <p/> <H3>Gene-Disease Validity track</H3> <P> The gene-disease validity classifications are labeled with the disease entity and hovering over the features shows the associated gene. Items are color coded based on the strength of their classification as provided below: </P> <table> <thead> <tr> <th style="border-bottom: 2px solid #6678B1;">Color</th> <th style="border-bottom: 2px solid #6678B1;">Classifications</th> </tr> </thead> <tbody><tr> <th bgcolor="#7800AA"></th> <td align="left"><b>Definitive:</b> The role of this gene in this particular disease has been repeatedly demonstrated and has been upheld over time</td> </tr> <tr> <th bgcolor="#000066"></th> <td align="left"><b>Strong:</b> The role of this gene in disease has been independently demonstrated typically in at least two separate studies, including both strong variant-level evidence in unrelated probands and compelling gene-level evidence from experimental data</td> </tr> <tr> <th bgcolor="#0000FF"></th> <td align="left"><b>Moderate:</b> There is moderate evidence to support a causal role for this gene in this disease, typically including both several probands with variants and moderate experimental data supporting the gene-disease assertion</td> </tr> <tr> <th bgcolor="#9999FF"></th> <td align="left"><b>Limited:</b> There is limited evidence to support a causal role for this gene in this disease, such as few probands with variants and limited experimental data supporting the gene-disease assertion</td> </tr> <tr> <th bgcolor="#6E6E6E"></th> <td align="left"><b>Animal Model Only:</b> There are no published human probands with variants but there is animal model data supporting the gene-disease assertion</td> </tr> <tr> <th bgcolor="#000000"></th> <td align="left"><b>No Known Disease Relationship:</b> Evidence for a causal role in disease has not been reported</td> </tr> <tr> <th bgcolor="#FF9933"></th> <td align="left"><b>Disputed:</b> Conflicting evidence disputing a role for this gene in this disease has arisen since the initial report identifying an association between the gene and disease</td> </tr> <tr> <th bgcolor="#FF3333"></th> <td align="left"><b>Refuted:</b> Evidence refuting the role of the gene in the specified disease has been reported and significantly outweighs any evidence supporting the role</td> </tr> </tbody></table> <P> The version of the <b>ClinGen Standard Operating Procedures (SOPs)</b> that each gene-disease classification was performed with is provided as well. An older or newer SOP version does not necessarily mean the classification is any more or less valid but is provided for clarity. Each details page also contains a direct link to an evidence summary detailing the rationale behind the specific classification and information such as a breakdown of the semi-qualitative framework, relevant PubMed IDs, the type of data (Genetic vs Experimental Evidence), and a detailed summary. </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>. </p> <H3>ClinGen VCEP Specifications track</H3> <p> Item names correspond to the VCEP loci, usually the gene symbol. Mouseovers display the disease with a link to the CSpec, the VCEP panel with a link to the ClinGen VCEP page, and the current expert panel status.</p> <h2>Data Updates</h2> Our programs check every day if ClinGen has an updated data file, and if so, update the track with the latest file. Click the "Data Format" on this track documentation page to see when the track was last updated. <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 <a href="/goldenPath/help/api.html">REST API</a>. 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> <p> Data is also freely available on the ClinGen website <a href="https://search.clinicalgenome.org/kb/gene-validity/" target="_BLANK">(gene-disease curation methods)</a> and FTP <a href="https://ftp.clinicalgenome.org/" target="_BLANK">(dosage curations)</a>. </p> <h2>Credits</h2> <p> Thank you to ClinGen and NCBI, especially Erin Rooney Riggs, Christa Lese Martin, Tristan Nelson, May Flowers, Scott Goehringer, and Phillip Weller for technical coordination and consultation, and to Christopher Lee, Luis Nassar, and Anna Benet-Pages of the Genome Browser team. </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> +Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E +<em>et al</em>. +<a href="https://linkinghub.elsevier.com/retrieve/pii/S1098-3600(21)03031-8" target="_blank"> +Standards and guidelines for the interpretation of sequence variants: a joint consensus +recommendation of the American College of Medical Genetics and Genomics and the Association for +Molecular Pathology</a>. +<em>Genet Med</em>. 2015 May;17(5):405-24. +PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/25741868" target="_blank">25741868</a>; PMC: <a +href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544753/" target="_blank">PMC4544753</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> -<p> -Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E -<em>et al</em>. -<a href="https://linkinghub.elsevier.com/retrieve/pii/S1098-3600(21)03031-8" target="_blank"> -Standards and guidelines for the interpretation of sequence variants: a joint consensus -recommendation of the American College of Medical Genetics and Genomics and the Association for -Molecular Pathology</a>. -<em>Genet Med</em>. 2015 May;17(5):405-24. -PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/25741868" target="_blank">25741868</a>; PMC: <a -href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544753/" target="_blank">PMC4544753</a> -</p>