ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5274T>A (p.Ser1758=) (rs199600387)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131241 SCV000186198 benign Hereditary cancer-predisposing syndrome 2014-10-01 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
Invitae RCV000198344 SCV000252930 benign Familial adenomatous polyposis 1 2019-12-31 criteria provided, single submitter clinical testing
Counsyl RCV000198344 SCV000488414 likely benign Familial adenomatous polyposis 1 2016-03-22 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000502224 SCV000591189 benign not specified criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000502224 SCV000600112 benign not specified 2017-06-19 criteria provided, single submitter clinical testing
Color RCV000131241 SCV000681726 likely benign Hereditary cancer-predisposing syndrome 2016-06-13 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679064 SCV000805428 likely benign not provided 2017-01-12 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679064 SCV000887535 benign not provided 2017-06-19 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000502224 SCV001361365 likely benign not specified 2019-01-25 criteria provided, single submitter clinical testing Variant summary: APC c.5274T>A alters a non-conserved nucleotide resulting in a synonymous change. Several computational tools predict a significant impact on normal splicing: four predict the variant creates a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0002 in 281872 control chromosomes, predominantly within the Non-Finnish European subpopulation at a frequency of 0.0004 in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 5.6 fold of the estimated maximal expected allele frequency for a pathogenic variant in APC causing Familial Adenomatous Polyposis phenotype (7.1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.5274T>A in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (1x) / likely benign (4x). Based on the evidence outlined above, the variant was classified as likely benign.

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.