bbd23e87bdbc50a9ee58c32982ff7987cb943af6 lrnassar Tue Sep 3 08:58:25 2024 -0700 Removing these tracks from internal trackDb since they are to be released only as public hubs refs #34352 diff --git src/hg/makeDb/trackDb/human/enigma.html src/hg/makeDb/trackDb/human/enigma.html deleted file mode 100644 index e8d65a8..0000000 --- src/hg/makeDb/trackDb/human/enigma.html +++ /dev/null @@ -1,145 +0,0 @@ -

Description

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NOTE:
-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. -

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-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. -
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-No attempt to identify individual patients should -be undertaken. No one is authorized to attempt to identify patients -by any means. -
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-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).

-The data required for the application of these ENIGMA codes are displayed in 5 data tracks:

BRCA1/BRCA2 protein domains 1.1.0 - -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. -
BRCA1/BRCA2 exon weights 1.1.0 - -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. -
BRCA1/BRCA2 functional assays 1.1.0 - -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. -
BRCA1/BRCA2 splicing 1.1.0 - -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. -
BRCA1/BRCA2 likelihood for PP4 and BP5 - -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. -

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Display Conventions

BRCA1/BRCA2 protein domains 1.1.0 - -Items in red show clinically relevant -protein domains. Mouseover on items shows the name of the domain and the location. -
BRCA1/BRCA2 exon weights 1.1.0 - -Mouseover on exons (black items) shows the transcript, exon number, and the PM5_PTC code strength. -
BRCA1/BRCA2 functional assays 1.1.0 - -Variants assigned with BS3 code are displayed in green, -PS3 code in red, or no code assigned in black. -Mouseover on items show variant HGVS nomenclature, assigned ACMG code and code weight. -
BRCA1/BRCA2 splicing 1.1.0 - -Items show variant positions, red indicates -exon deletions, blue 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. -
BRCA1/BRCA2 likelihood for PP4 and BP5 - -Variants assigned with PP4 code are displayed in red, BP5 code -in green, 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. -

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Data Access

-The most up-to-date VCEP specifications for the application of ACMG/AMP criteria -for BRCA1 and BRCA2 genes are freely available at the ClinGen -Criteria Specification (CSpec) Registry. This registry is intended to -provide access to the Criteria Specifications used and applied by ClinGen -Variant Curation Expert Panels and biocurators in the classification of variants. -

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Methods

-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 github. -

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Credits

-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.

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References

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-Enigma Guidelines: https://clinicalgenome.org/affiliation/50087/

-Enigma Consortium: https://enigmaconsortium.org/

-Parsons MT, Tudini E, Li H, Hahnen E, Wappenschmidt B, Feliubadaló L, Aalfs CM, Agata S, -Aittomäki K, Alducci E et al. - -Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA -resource to support clinical variant classification. -Hum Mutat. 2019 Sep;40(9):1557-1578. -PMID: 31131967; PMC: PMC6772163 -