Submissions for variant NM_000038.6(APC):c.-2_135+1274del

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355291	SCV001550134	pathogenic	Familial adenomatous polyposis 1		no assertion criteria provided	clinical testing	The APC c.-85-?_1408+?del variant (chr:5 g.112073556_112157688delGRCh37) results in a deletion of promoter regions 1A,1B, 5’UTR, and exons 1 through 10, although the precise breakpoints of this deletion were not determined, nor were the effects of this variant on the resulting mRNA or protein product determined. The variant was identified in the literature in 1 of 2332 proband chromosomes from individuals or families with familial adenomatous polyposis (Aretz 2005, Friedl 2005). The variant was identified in LOVD 3.0 (1x as pathogenic). The c.-85-?_1408+?del variant was not identified in the dbSNP, ClinVar, and UMD-LSDB databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The variant was identified by our laboratory in 1 individual with desmoids and multiple colorectal adenomas. This alteration would typically be predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the APC gene are an established mechanism of disease in familial adenomatous polyposis and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic.