Annotation Sources¶

As a warehouse, AnFiSA stores annotations of single nucleotide variants (SNP), insertions and deletions, copy number variantions (CNV), and structural variations (SV) in the human genome that are used to prioritize candidate pathogenic variants in an affected proband. Some of the annotations reflect technical information such as provenance and confidence information about the specific call (call annotations). Other annotations summarize genetic and biological evidence relevant to the potential effect of mutations on molecular function and phenotype (biological annotations). These annotations combine multiple inputs and consist of genomic, protein, and disease-specific information gathered from different public and proprietary sources.

Brief description of annotation sources¶

AnFiSA relies on dbNSFP gnomAD, ENSEMBLE Variant Effect Predictor (VEP), and NCBI resources (e.g., ClinVar, MedGen, and PubMed), OMIM, SpliceAI, and HGMD as main annotation sources. Collectively, these sources provide information on the phenotypic effects of genes and individual variants, allele frequencies, functional effect predictors (e.g., SIFT, PolyPhen), and conservation scores (e.g. PhastCons and GERP).

For ClinVar, in addition to the usual data for each variant including clinical significance, stars, review status, conflicts, etc., the user has the option to select a set of trusted submitters, in which case the clinical significance assigned by them will be provided as a separate category. By default, AnFiSA includes Laboratory of Molecular Medicine (LMM), GeneDx, and Invitae as trusted sources by our team, though designation as trusted can be customized.

Here is the list of sources used in annotation process in AnFiSA system.