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Table 2 Summary of tools for germline variant prioritization in pedigrees

From: Pedigree based DNA sequencing pipeline for germline genomes of cancer families

Tools Details References
Familial cancer variant prioritization pipeline (FCVPP) Gives guidelines for identification of disease causing variants based on segregation in the family pedigrees of cancer and in silico predictions for deleteriousness of all types of variants in whole-genome data. Evaluates each family individually based on phenotype and sample availability from the family members. Current article
VAR-MD Provides a ranked list of variants using Mendelian inheritance models, predicted pathogenicity annotation based on evolutionary sequence conservation and allele frequency data for small Mendelian-type of families with whole-exome data. Sincan et. al. (2012) [41]
KGGSeq Combines gene (identity-by-descent, linkage, inheritance model), variant (allele frequency, non-synonymous, disease-causing) and knowledge (protein-protein interaction, biological pathway, phenotype) level information to prioritize exome variants in disease families. Li et. al. (2012) [42]
Annotate-it Integrates data of coding variants, genes and samples from different sources providing filtering options for e.g. pedigree data. Sifrim et. al. (2013) [43]
FAVR (Filtering and Annotation of Variants that are Rare) After variant annotation, filtering for rare and likely deleterious coding variants according to in silico tools; pedigree information is used at the end step. Pope et. al. (2013) [44]
PriVar After variant annotation, filtering for deleterious variants based on several in silico tools, at the end different family-based criteria (e.g. linkage, inheritance model). Zhang et. al. (2013) [45]
VariantDB Integrates sample (e.g. family-based inheritance models) and variant (e.g. allele frequency, pathogenicity and function) annotations from diverse tools and provides gene and family/cohort based filtering possibilities. Vandeweyer et. al. (2014) [46]
pVAAST (pedigree-Variant Annotation, Analysis and Search Tool) A VAAST implementation for family-based data based on the composite likelihood ratio test (CLRTv) combines linkage analysis, allele frequency differences for cases vs. controls and phylogenetic conservation and biochemical function of the variant; takes incomplete penetrance and locus heterogeneity into account. Gives a ranking of genes/variants. Hu et. al. (2014) [39]
FamAnn (Family Annotation) After variant annotation of whole-genome data uses pedigree data to provide variants segregating in the family. Provides in silico predictions for deleteriousness in excel format to user for further prioritization. No recommendations for downstream prioritization strategies are provided. Yao et. al. (2014) [38]
BiERapp Integrates pedigree information with in silico predictions for exome variants. Aleman (2014) [47]
FamPipe Provides annotation of variants shared by affected family members using imputation identity-by-descent, linkage and disease model identification modules, however requires user-provided data for population allele frequencies and functional annotation of the variants for variant prioritization. Chung et. al. (2016) [48]