ClinVar Miner

Submissions for variant NM_000038.6(APC):c.646-1G>C

dbSNP: rs78847145
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000500268 SCV000591045 pathogenic not provided no assertion criteria provided clinical testing The c.646-1G>C variant has not been reported in the literature nor previously identified by our laboratory. This variant is predicted to cause abnormal splicing because the nucleotide substitution occurs in the invariant region of the splice consensus sequence. In addition, in-silico or computational prediction software (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predicts a difference in splicing in 5 of 5 different programs, increasing the likelihood this variant is pathogenic. A different nucleotide change at the same position (c.646-1G>A) has been previously observed in one study in an individual with clinical features of FAP and they demonstrated that this variant abrogates the canonic splice-acceptor site of exon 6, leading to the activation of a cryptic “AG” splice-acceptor site by analyses of the cDNA and increasing the likelihood that the c.646-1G>C variant also has a functional consequence (Aceto 2005). Furthermore, this variant is of the type which is expected to cause the disorder. In summary, based on the above information, this variant is classified as Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.