melissacline
commented
2 months ago For the first blurb, some of the earlier text is now outdated. Here is an updated version:
The Allele Frequency Reference Sets tile shows the frequency of a BRCA1 or BRCA2 variant in a reference population from the gnomAD resource. Allele Frequencies can be helpful in understanding the frequency at which a variant appears in the population, and whether there is a population in which the variant is so common that it's not likely to increase the risk of a much less common disease. Different sets (exome, genome) are shown in different subtiles. To view or collapse all subtiles, click the arrows at the top right of the tile on the Variant Details Page.
Under the ACMG/AMP Standards and Guidelines, variant curators can assign specific evidence codes to variants according to their frequency in reference populations. These evidence codes contribute to the curation of the variants as Benign, Pathogenic, Likely Benign, or Likely Pathogenic.
(Text for the slightly longer description) The ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel (VCEP) has published the definitive rules for curating BRCA variants. These rules are based on the ACMG/AMP framework but further specialized for the nuances of the BRCA genes and Hereditary Breast and Ovarian Cancer syndrome. One portion of these rules describes how and when population frequencies can translate to specific ACMG evidence for variant curation, considering the frequencies, the type and location of the variant, and technical data that describe the reliability of the observed population frequencies, such as read depth and heuristic flags. To aid in the curation of BRCA variants, by the VCEP as well as other curators, we have derived the provisional ACMG population frequency evidence codes for all variants in BRCA Exchange. Note that by ClinGen's procedures, all variant evidence must be reviewed by specialized biocurators as part of the variant curation process. Most of the evidence codes shown here have not yet been reviewed, therefore they are marked as provisional and should be viewed with appropriate caveats. Anyone wishing to verify a provisional evidence code can review the original data from gnomAD together with the VCEP rules for population frequencies.
e-t-k
As part of adding a Provisional Evidence subtile, we want to add a description to the Allele Frequency Reference Sets Tile help section.
Here's the current draft, including the locations where text could be added. @melissacline , can you please draft text for either of both of these placeholders?
The Allele Frequency Reference Sets tile shows the frequency of a BRCA1 or BRCA2 variant in a reference population. Allele Frequencies can be helpful in understanding the frequency at which a variant appears in the population, and whether there is a population in which the variant is more common and therefore not likely to increase the risk of disease. Different sets are shown in different subtiles. To view or collapse all subtiles, click the arrows at the top right of the tile on the Variant Details Page.
BRCA Exchange has standardized on gnomAD as its source of allele frequency reference data. The earlier allele frequency reference sets, ExAC, ESP, and 1000 Genomes, have mostly been subsumed by gnomAD. We have retired the display of these earlier datasets, but still retain their data in our database for historical puposes.
Insert short sentence about provisional evidence. | Provisional ACMG Variant Evidence | Insert slightly longer description of the provisional evidence.
- Provisional Code The provisional ACMG population frequency evidence code, as estimated according to rules of the ClinGen Variant Curation Expert Panel.
- Description Details on how the provisional ACMG population frequency evidence code was determined. | > gnomAD: Genome Aggregation Database (non-cancer cohort)