ClinVar Miner

Submissions for variant NM_000038.6(APC):c.532-8G>A (rs1060503323)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000458868 SCV000552641 likely pathogenic Familial adenomatous polyposis 1 2016-11-14 criteria provided, single submitter clinical testing This sequence change falls in intron 5 of the APC gene. It does not directly change the encoded amino acid sequence of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in two affected individuals in a single family with familial adenomatous polyposis (FAP). Although additional family members were not genotyped, this family includes eight affected individuals across three generations (PMID: 19196998). Experimental in vitro RT-PCR and ex vivo minigene studies have shown that this intronic change severely diminishes normal splicing at the consensus splice site, while creating and utilizing a novel acceptor splice site 6 nucleotides upstream of the consensus acceptor splice site, leading to the incorporation of a premature stop codon within these additional sequences (PMID: 19196998, 24599579). In summary, this variant is a rare intronic change that has been reported to segregate with disease in a family with FAP, and shown to disrupt normal APC splicing. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ambry Genetics RCV000491376 SCV000579793 pathogenic Hereditary cancer-predisposing syndrome 2015-09-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Functionally-validated splicing mutation,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000503571 SCV000591038 pathogenic Familial adenomatous polyposis criteria provided, single submitter clinical testing

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.