This is to be used when there is an incomplete trio or when there is described family history for all/some of the clinical features.
The rules for non-trio screening are defined in attached text file "r0.3_non-trios_June2016.txt"
pDNM KnownVar: Possibly denovo mutation is a singleton and has been previously reported as pathogenic
pDNM KnownVar <5 Alleles: Possibly denovo mutation was observed less than five times in controls and has been previously reported as pathogenic
Tier 2 pDNM LoF: Possibly denovo mutation was observed less than five times in controls and is a LoF variant in a gene with known pathogenic LoF function variants
Tier 2 pREC LoF: Possibly newly recessive homozygous functional variants in a gene with known pathogenic LoF function variants
Tier 2 pCHET LoF: Possibly compound het LoF variants that both are found in a gene with known pathogenic LoF function variants
The code to run non-trio rules on ATAV variant output requires users have access to the R statistical package.
1) Ensure that both files "r0.3_filters_nontrio.R" and "r0.3_filters_nontrio_details.R" are in the same directory as the ATAV .csv output from Recommended_ATAV_Commands.
2) Open "r0.3_filters_nontrio_details.R" in a text editor and update all relevant directories.
3) Open and execute "r0.3_filters_nontrio_details.R" in R statistical package.
4) Results will be published per non-trio screen into the directory where the R files and ATAV.csv files were housed.
The results are four categories:
Lists variants that are absent among controls and where:
1) the precise same variant has been reported 'pathogenic' in available literature,
2) or, a variant within 2 flanking bases has been reported in available literature,
3) or, for indels, either the precise indels (HGMD) or indel(s) within 9 flanking bases of start coordinate have been previously reported as 'pathogenic' (ClinVar).
As above, but the variant is allowed to be present up to five times among controls (Tier 2).
Variant is predicted to result in a loss-of-function effect occurs within a gene reported to cause disease through LoF alleles. These variants are permitted to be present up to 5 times among controls (Tier 1 and Tier 2).
Focusing on homozygous / hemizygous genotypes where the precise same variant has been reported as pathogenic OR a recessive LoF variant observed in a known LoF disease gene.