106ce8e3a43c932f7a6485f81935620e0a21cf70 lrnassar Wed Mar 13 13:56:47 2024 -0700 Grammar corrections from CR feedback, refs #33223 diff --git src/hg/makeDb/trackDb/human/enigma.html src/hg/makeDb/trackDb/human/enigma.html index 60d1cbe..e8d65a8 100644 --- src/hg/makeDb/trackDb/human/enigma.html +++ src/hg/makeDb/trackDb/human/enigma.html @@ -31,91 +31,91 @@ 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) +This track shows exon-specific weights for the PM5_PTC ACMG code and is used +for the application of 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 +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. +Mouseover on exons (black items) shows 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>, +Variants assigned with BS3 code are displayed 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 +exon deletions, <b><font color="blue">blue</font></b> exon duplications, and 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. +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 +Variants assigned with PP4 code are displayed 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 +The most up-to-date VCEP specifications for the 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>.