ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1409-2A>G (rs1064794163)

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
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000606942 SCV000731722 likely pathogenic Familial multiple polyposis syndrome 2017-11-02 criteria provided, single submitter clinical testing The c.1409-2A>G variant in APC has been reported in 1 individual with familial a denomatous polyposis (FAP, LMM unpublished data), in at least 1 individual with attenuated FAP (Aretz 2004, Friedl 2005), and was absent from large population s tudies. This variant occurs in the invariant region (+/- 1,2) of the splice cons ensus sequence and has been observed to cause skipping of exon 11 of APC (Aretz 2004), resulting in a truncated protein that is lacking 32 amino acids. Other va riants at this splice site have been reported in the Human Gene Mutation Databas e (HGMD) in association with FAP, one affecting the same nucleotide and two affe cting the -1 position (Stenson 2017). In summary, while additional studies are r equired to fully establish its clinical significance, the c.1409-2A>G variant is likely pathogenic. ACMG/AMP criteria applied: PM2, PM4, PP3, PS4_Supporting (Ri chards 2015).

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.