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Non-Trio Rules

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.

Steps:
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:
kv.csv : 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).

kv_5alleles.csv : As above, but the variant is allowed to be present up to five times among controls (Tier 2).

private_lof.csv : Variant is predicted to result in a loss-of-function effect and 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).

rec_kv_lof.csv : 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.