3f6d3b9b6ecc50930f78bc9ce752b0b0950590d5 lrnassar Mon Mar 11 09:58:47 2024 -0700 Adding enigma tracks html page, refs #32914 diff --git src/hg/makeDb/trackDb/human/enigma.html src/hg/makeDb/trackDb/human/enigma.html new file mode 100644 index 0000000..60d1cbe --- /dev/null +++ src/hg/makeDb/trackDb/human/enigma.html @@ -0,0 +1,145 @@ +<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 tracks listed here contain data from the ClinGen ENIGMA BRCA1 and BRCA2 +Expert Panel Specifications to the ACMG/AMP Variant Interpretation +Guidelines for BRCA1/BRCA1 Version 1.0.0. The ENIGMA VCEP has adapted +the ACMG-AMP codes for the BRCA1 and BRCA2 genes. These include the +codes PVS1 (modified PVS1 decision tree), PS3/BS3 (functional data), +PP4/BP5 (multifactorial data), PM5_PTC (PTC data, at exon level), +the (potentially) clinically important functional domains defined by +ENIGMA, and prediction programs (SpliceAI and BayesDel for PP3/BP4).<br><br> +The data required for the application of these ENIGMA codes are displayed in 5 data tracks:</p> +<p> +<ul> +<li><b>BRCA1/BRCA2 protein domains 1.1.0</b> - +Shows the (potentially) clinically important functional domains for +the genes BRCA1 and BRCA2 as defined by ENIGMA. Data taken from Figure +1 of the guidelines document CSpec_BRCA12ACMG-Rules-Specifications_V1.0_23-04-27. +</li> +<li><b>BRCA1/BRCA2 exon weights 1.1.0</b> - +This track shows exon-specific weights for PM5_PTC ACMG code used +for application of this code for novel protein termination codon (PTC) +variants in an exon where a different proven pathogenic PTC variant +has been seen before. Data taken from guidelines document +CSpec_BRCA12ACMG_Rules-SupplementaryTables_V1.0_23-04-27. +</li> +<li><b>BRCA1/BRCA2 functional assays 1.1.0</b> - +Summary of BRCA1 and BRCA2 functional assay results reviewed for +application of PS3 and BS3 ACMG codes Data taken from guidelines +document CSpec_BRCA12ACMG-Rules-Specifications_V1.0_Table-9_23-04-27. +</li> +<li><b>BRCA1/BRCA2 splicing 1.1.0</b> - +Summary of ACMG codes applicable for variants considered against +the BRCA1 and BRCA2 PVS1 decision trees. Includes PVS1 and PM5 +codes recommended for initiation, nonsense/frameshift, deletion, +duplication, and splice site (donor/acceptor ±1,2) variants– +organized by exon. Data taken from guidelines document +CSpec_BRCA12ACMG-Rules-Specifications_V1.0_Table-4_23-04-27. +</li> +<li><b>BRCA1/BRCA2 likelihood for PP4 and BP5</b> - +Summary of BRCA1 and BRCA2 multifactorial likelihood analysis +scores (displayed as Combined LR score) for ACMG codes PP4 and BP5. +Data taken from Parsons et al. 2019 suppl table HUMU-40-1557-s001_Parson_Multicatorial.xlsx. +</li> +</ul> +</p> + +<h2>Display Conventions</h2> +<p> +<ul> +<li><b>BRCA1/BRCA2 protein domains 1.1.0</b> - +Items in <b><font color="red">red</font></b> show clinically relevant +protein domains. Mouseover on items shows the name of the domain and the location. +</li> +<li><b>BRCA1/BRCA2 exon weights 1.1.0</b> - +Mouseover on exons (black items) show the transcript, exon number and the PM5_PTC code strength. +</li> +<li><b>BRCA1/BRCA2 functional assays 1.1.0</b> - +Variants assigned with BS3 code in <b><font color="green">green</font></b>, +PS3 code in <b><font color="red">red</font></b>, or no code assigned in black. +Mouseover on items show variant HGVS nomenclature, assigned ACMG code and code weight. +</li> +<li><b>BRCA1/BRCA2 splicing 1.1.0</b> - +Items show variant positions, <b><font color="red">red</font></b> indicates +exon deletions, <b><font color="blue">blue</font></b> exon duplications, purple +items indicate variants with supporting RNA-based functional evidence. Mouseover +on items show transcript, exon, variant position, possible variant type at +that position and assigned ACMG code to the variant. +</li> +<li><b>BRCA1/BRCA2 likelihood for PP4 and BP5</b> - +Variants assigned with PP4 code in <b><font color="red">red</font></b>, BP5 code +in <b><font color="green">green</font></b>, and non-informative variants (no code +assigned) in grey. Mouseover on items show variant HGVS nomenclature, combined +likelihood ratio (LR) score, and assigned ACMG code and strength. +</li> +</ul> +</p> + +<h2>Data Access</h2> +<p> +The most up-to-date VCEP specifications for application of ACMG/AMP criteria +for BRCA1 and BRCA2 genes are freely available at the <a target="_blank" +href="https://cspec.genome.network/cspec/ui/svi/affiliation/50087">ClinGen +Criteria Specification (CSpec) Registry</a>. This registry is intended to +provide access to the Criteria Specifications used and applied by <a +target="_blank" href="https://clinicalgenome.org/affiliation/vcep/#ep_table_heading">ClinGen +Variant Curation Expert Panels</a> and biocurators in the classification of variants. +</p> + +<h2>Methods</h2> +<p> +These data were created and adapted from the files referenced above. Some custom +scripting was employed in tasks like mapping variants, adding colors and +mouseovers, and producing the desired format. For the complete details on +the data processing see the makedoc on our <a target="_blank" +href="https://github.com/ucscGenomeBrowser/kent/blob/master/src/hg/makeDb/doc/enigma.txt">github</a>. +</p> + +<h2>Credits</h2> +<p> +Thank you to Luis Nassar from the Genome Browser team, Anna Benet-Pagès +and Andreas Laner for technical coordination and consultation, and to +the ENIGMA consortia for making these data available.</p> + +<h2>References</h2> + +<p> +Enigma Guidelines: <a target="_blank" href="https://clinicalgenome.org/affiliation/50087/">https://clinicalgenome.org/affiliation/50087/</a></p> +<p> +Enigma Consortium: <a target="_blank" href="https://enigmaconsortium.org/">https://enigmaconsortium.org/</a></p> +<p> +Parsons MT, Tudini E, Li H, Hahnen E, Wappenschmidt B, Feliubadaló L, Aalfs CM, Agata S, +Aittomäki K, Alducci E <em>et al</em>. +<a href="https://doi.org/10.1002/humu.23818" target="_blank"> +Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA +resource to support clinical variant classification</a>. +<em>Hum Mutat</em>. 2019 Sep;40(9):1557-1578. +PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/31131967" target="_blank">31131967</a>; PMC: <a +href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6772163/" target="_blank">PMC6772163</a> +</p>