by_gene

--by_gene report

By using the tag --by_gene with the analyse or sort option, you will generate a report that will group variants by gene.

Each gene will be assigned a "mutational burden" score that is useful to assess how much this gene is affected by variants in a cohort (if the input file is a multi-sample vcf).

The gene burden score is the sum of the probability of pathogenicity (0.8 and above otherwise excluded) or variant i multiplied by the number of individuals affected by variant i.

A warning will be associated if the genes is a FLAG genes (frequently mutated in exome studies), if the number of sample affected seems to be to high (half of the variants in a gene with more than half of the individuals affected) or if the gene is especially long (more than 250,000bp, which are expected to harbour more variants).

This report is useful to detect genes frequently mutated in a cohort sharing a same phenotype (but where several different variants are present).

Example

ERCC2	50.726
Chr	Start	End	Ref	Alt	Allele	ExonicFunc.refGene	Probability_Path	Prediction_ACMG_tapes	Samples
19	45867550	45867550	C	T	T	missense_variant	0.9993	Pathogenic	Sample_12, Sample_15, Sample_18, Sample_21, Sample_24, Sample_27, Sample_28, Sample_34, Sample_35, Sample_37, Sample_38, Sample_40, Sample_41, Sample_42, Sample_45, Sample_47
19	45856371	45856371	G	A	A	missense_variant	0.9993	Pathogenic	Sample_12, Sample_15, Sample_18, Sample_21, Sample_24, Sample_27, Sample_28, Sample_34, Sample_35, Sample_37, Sample_38, Sample_40, Sample_41, Sample_42, Sample_45, Sample_47
19	45860626	45860626	G	C	C	missense_variant	0.9941	Pathogenic	Sample_12
19	45867532	45867532	C	T	T	missense_variant	0.9941	Pathogenic	Sample_16, Sample_36
19	45855805	45855807	CTG	CG	G	frameshift_variant	0.9941	Likely Pathogenic	Sample_27
19	45855574	45855574	G	A	A	missense_variant	0.9878	Likely Pathogenic	Sample_16, Sample_36
19	45860760	45860760	C	T	T	missense_variant	0.9878	Likely Pathogenic	Sample_3, Sample_23, Sample_31
19	45856059	45856059	C	G	G	missense_variant	0.8999	Likely Pathogenic
19	45860760	45860760	C	T	T	missense_variant	0.8121	VUS	Sample_21
19	45858047	45858047	C	T	T	missense_variant	0.8121	VUS	Sample_26
19	45868168	45868168	G	C	C	missense_variant	0.8121	VUS	Sample_3, Sample_21, Sample_23, Sample_27, Sample_31, Sample_32, Sample_45, Sample_46
19	45867139	45867139	T	C	C	missense_variant	0.8121	VUS	Sample_21