3f6d3b9b6ecc50930f78bc9ce752b0b0950590d5
lrnassar
Mon Mar 11 09:58:47 2024 -0700
Adding enigma tracks html page, refs #32914
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+Description
+
+
+
+
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.
+
+
+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.
+
+
+No attempt to identify individual patients should
+be undertaken. No one is authorized to attempt to identify patients
+by any means.
+
+
+
+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 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.
+
+- 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.
+
+
+
+
+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) show the transcript, exon number and the PM5_PTC code strength.
+
+- BRCA1/BRCA2 functional assays 1.1.0 -
+Variants assigned with BS3 code 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, 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 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.
+
+
+
+
+Data Access
+
+The most up-to-date VCEP specifications for 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.
+
+
+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.
+
+
+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.
+
+References
+
+
+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
+