A knowledge-based framework for the discovery of cancer-predisposing variants using large-scale sequencing breast cancer data

Table 1 Breast cancer-predisposing genes and variants found in our case dataset

Gene	Somatic driver gene	Total number of variants	Number of pathogenic variants	Number of truncating variants	Number of highly damaging mutations
ATM	X	21			5
BRCA1	X	18	2		3
BRCA2	X	21	5		2
BRIP1		5	1
CDH1	X	3	1
CHEK2	X	6	2	1
MRE11A		4			1
NBN		5	1	2
PALB2		1
PRKAR1A
PTEN	X
RAD50		5
RAD51C		3		1
STK11	X	3
TP53	X	4			1

The second column reports if the gene is also considered to be a somatic driver gene. The next three columns report the total number of non-synonymous variants, the number of variants considered being pathogenic, and the number of rare truncating variants (control minor allele frequency below 1%) not already included in the list of pathogenic variants. The last column shows instead all the missense variants that are not considered to be pathogenic but have a very high deleteriousness score (8/9 tools for predicting functional damage report the variant as damaging). As pathogenic reference we used the ClinVar and Humsavar databases

ISSN: 1465-542X