From 5866e487fd371abb6f787f850409489162f15239 Mon Sep 17 00:00:00 2001 From: E-T-K Date: Fri, 21 Jun 2024 23:50:04 +0000 Subject: [PATCH] update allele freq help per #1507 --- .../help/research/allele-frequency-provisional-evidence.md | 3 +-- .../help/research/allele-frequency-reference-sets.md | 6 ++---- 2 files changed, 3 insertions(+), 6 deletions(-) diff --git a/website/content/help/research/allele-frequency-provisional-evidence.md b/website/content/help/research/allele-frequency-provisional-evidence.md index 54abdff8c..9222fc9ef 100644 --- a/website/content/help/research/allele-frequency-provisional-evidence.md +++ b/website/content/help/research/allele-frequency-provisional-evidence.md @@ -1,5 +1,4 @@ - -ETK TODO discussion of the provisional evidence +The ClinGen ENIGMA _BRCA1_ and _BRCA2_ Variant Curation Expert Panel (VCEP) has published the definitive [rules](https://cspec.genome.network/cspec/ui/svi/affiliation/50087) 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](https://cspec.genome.network/cspec/ui/svi/affiliation/50087) for population frequencies. * #### Provisional Code ((Provisional_Evidence_Code_Popfreq)) The provisional ACMG population frequency evidence code, as estimated according to rules of the ClinGen Variant Curation Expert Panel. diff --git a/website/content/help/research/allele-frequency-reference-sets.md b/website/content/help/research/allele-frequency-reference-sets.md index 9b5c1a672..ad8c401d6 100644 --- a/website/content/help/research/allele-frequency-reference-sets.md +++ b/website/content/help/research/allele-frequency-reference-sets.md @@ -1,5 +1,3 @@ -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. +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. -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. - -ETK TODO Line about provisional evidence! +Under the [ACMG/AMP Standards and Guidelines](https://pubmed.ncbi.nlm.nih.gov/25741868/), 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.