ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6354_6356TGC[5] (p.Ala2122dup) (rs587780602)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000588527 SCV000166048 likely benign not provided 2019-03-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129306 SCV000184068 likely benign Hereditary cancer-predisposing syndrome 2017-07-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification,Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
GeneDx RCV000237032 SCV000292463 uncertain significance not specified 2017-03-29 criteria provided, single submitter clinical testing This duplication of three nucleotides in APC is denoted c.6363_6365dupTGC at the cDNA level and p.Ala2122dup at the protein level. The normal sequence, with the bases that are duplicated in brackets, is CTGC[dupTGC]ATGT. This in-frame duplication of a single Alanine residue is not located in a known functional domain (Azzopardi 2008, UniProt). This variant was reported in an individual undergoing multigene cancer panel testing due to a history of a Lynch syndrome-related cancer and/or polyps (Yurgelun 2015). APC Ala2122dup was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since in-frame duplications may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider APC Ala2122dup to be a variant of uncertain significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000237032 SCV000591198 uncertain significance not specified 2015-10-09 criteria provided, single submitter clinical testing
Color RCV000129306 SCV000681795 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-24 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588527 SCV000694090 benign not provided 2016-09-30 criteria provided, single submitter clinical testing Variant summary: The APC c.6363_6365dupTGC (p.Ala2121dup) variant involves the insertion of three nucleotides in a 5 alanine repeat region, resulting in an in-frame duplication of single Alanine. One in silico tool predicts a benign outcome for this variant. This variant was found in 36/121200 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0004797 (32/66714). This frequency is about 7 times the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. This variant has been reported in affected individuals without strong evidence of causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance/likely benign, all without evidence to independently evaluate. Taken together, this variant is classified as benign.
PreventionGenetics,PreventionGenetics RCV000588527 SCV000805452 uncertain significance not provided 2017-08-24 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.