ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1959G>A (p.Arg653=) (rs72541809)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 15
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000120034 SCV000167000 benign not specified 2014-01-03 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000128958 SCV000172839 benign Hereditary cancer-predisposing syndrome 2014-12-12 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;Intronic alteration with no splicing impact by rt-pcr analysis or other splicing assay;Co-occurence with mutation in same gene (phase unknown)
Invitae RCV000987561 SCV000252579 benign Familial adenomatous polyposis 1 2019-12-31 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000239214 SCV000297017 benign Familial multiple polyposis syndrome 2015-10-19 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000340009 SCV000451995 benign APC-Associated Polyposis Disorders 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120034 SCV000591102 benign not specified 2013-01-21 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000120034 SCV000593257 likely benign not specified 2016-08-18 criteria provided, single submitter clinical testing
Color RCV000128958 SCV000681499 benign Hereditary cancer-predisposing syndrome 2016-03-17 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586895 SCV000694006 benign not provided 2016-06-20 criteria provided, single submitter clinical testing Variant summary: The APC c.1959G>A (p.Arg653Arg) variant involves the alteration of a conserved nucleotide one nucleotide downstream from the intron-exon boundary, resulting in a synonymous change. 4/5 splice prediction tools predict no significant impact on normal splicing. Consistent with these predictions, in vitro as well as ex vivo analysis shows that this variant does not cause abnormal splicing (Aretz_2004, Grandval_2014). This variant was found in 538/119468 control chromosomes (including 6 homozygotes), predominantly observed in the European (Finnish), subpopulation at a frequency of 0.0323708 (213/6580). This frequency is about 453 times greater than the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714), suggesting this is a benign polymorphism found primarily in the populations of European (Finnish) origin. This variant has also been reported in several FAP patients (Aretz_2004, Stekrova_2007, Grandval_2014, UMD); however, some patients also carried another deleterious variant in the same gene, strongly suggesting for the benign outcome. In addition, multiple clinical diagnostic laboratories and one reputable database have classified this variant as benign. Taken together, this variant is classified as Benign.
PreventionGenetics,PreventionGenetics RCV000120034 SCV000805375 benign not specified 2016-11-02 criteria provided, single submitter clinical testing
Mendelics RCV000987561 SCV001136888 likely benign Familial adenomatous polyposis 1 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000120034 SCV001158623 benign not specified 2019-01-23 criteria provided, single submitter clinical testing
ITMI RCV000120034 SCV000084166 not provided not specified 2013-09-19 no assertion provided reference population
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000120034 SCV000256937 benign not specified no assertion criteria provided research
True Health Diagnostics RCV000128958 SCV000693473 likely benign Hereditary cancer-predisposing syndrome 2017-11-10 no assertion criteria provided 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.