AMP/ASCO/CAP tier classification for somatic variants in cancer

Function that assigns tier classifications to genes subject to somatic CNA (amplifications and deletions), somatic SNVs/InDels, or RNA fusions, based on the presence and strength of biomarker evidence associated with records in the variant set. Tier classification is based on the AMP/ASCO/CAP guidelines for somatic variant interpretation in cancer (Li et al., J Mol Diagn. 2017). The function also considers variant properties associated with oncogenes and tumor suppressor genes (e.g. low MAF, coding status), which are used to assign tier 3 status to variants with uncertain clinical significance.

Usage

assign_amp_asco_cap_tiers(
  vartype = "snv_indel",
  clinical_significance = "therapeutic_sensitivity",
  primary_site = "Any",
  biomarker_mapping_confidence = "medium",
  var_df = NULL,
  biomarker_items = NULL
)

Arguments

vartype

variant type ('snv_indel', 'cna', 'fusion')

clinical_significance

character indicate the clinical significance types of evidence used for tiering of predictive evidence. Possible values: "therapeutic_sensitivity", "therapeutic_resistance", "prognostic_poor", "prognostic_better", "diagnostic_positive", "diagnostic_negative"

primary_site

primary tumor site

biomarker_mapping_confidence

confidence level of variant-biomarker mapping resolution (e.g. 'high' or 'medium'). 'High' indicates matches at genomic/hgvsp/hgvsc level, 'medium' indicates matches at gene/exon level Note that that matches at gene/exon level also consider variant properties (loss-of-function, hotspot overlap etc) to avoid noise from presumably less impactful variants that are likely not relevant for the biomarker relationship

var_df

data frame with variants (SNVs/InDels, CNAs, fusions)

biomarker_items

data frame with biomarker evidence items