ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7862C>G (p.Ser2621Cys) (rs72541816)

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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000077995 SCV000109833 benign not specified 2013-09-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130974 SCV000185889 benign Hereditary cancer-predisposing syndrome 2014-11-28 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
PreventionGenetics,PreventionGenetics RCV000077995 SCV000301607 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000367966 SCV000452050 benign APC-Associated Polyposis Disorders 2018-03-06 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.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000034401 SCV000511737 likely benign not provided 2017-01-24 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Invitae RCV000987588 SCV000562659 benign Familial adenomatous polyposis 1 2020-12-07 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000077995 SCV000593260 benign not specified 2019-10-16 criteria provided, single submitter clinical testing
Color Health, Inc RCV000130974 SCV000681891 benign Hereditary cancer-predisposing syndrome 2016-03-21 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283419 SCV000885018 benign none provided 2019-10-29 criteria provided, single submitter clinical testing
Mendelics RCV000987588 SCV001136953 likely benign Familial adenomatous polyposis 1 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000034401 SCV001154486 uncertain significance not provided 2017-05-01 criteria provided, single submitter clinical testing
GeneDx RCV000034401 SCV001830306 benign not provided 2015-03-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24728327, 27153395, 1316610, 24082139, 21859464, 24599579, 25260786, 22703879)
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034401 SCV000043143 no known pathogenicity not provided 2012-07-13 no assertion criteria provided research Converted during submission to Benign.
ITMI RCV000077995 SCV000084165 not provided not specified 2013-09-19 no assertion provided reference population
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353889 SCV000591216 benign Carcinoma of colon no assertion criteria provided clinical testing The p.Ser2621Cys variant has been previously reported in the literature. From selected publications it was identified in 7 if 2428 case chromosomes (frequency: 0.0028) and 21 of 3670 control chromosomes (frequency: 0.0057), increasing the likelihood this is a benign polymorphism (Miyoshi_1992_1316610, Scott_2004_2839999, Ruiz-Ponte_2001_11668620, Azzopardi_2008_18199528, Lefevre_2012_22875147). In addition, it is reported with a frequency of 126/2172 control chromosomes from the 1000 genomes project and at a frequency of 0.005 in the European gohort ESP project database (dbSNPiD: rs72541816). Furthermore, 2 studies demonstrated non-segregation (Scott_2004_2839999, Ruiz-Ponte_2001_11668620) and the frequency of this variant was reported as higher in controls vs cases in two studies (Cancer Res-2008-Azzopardi-358-63_18199528, Lefevre_2012_jhg201299a_22875147), increasing the likelihood that this variant is benign. This variant is conserved in mammals but not lower organisms although it appears to not be located in an important functional domain, the creation of cystein residues, having a higher propensity for generating disulphide bonds, could in theory impact the protein. Computational analysis using several programs (SIFT, AlignGVGD, Polyphen-2, BLOSUM), do not agree on the imapact this variant change may have, and this information is not very predictive of pathogenicity. Based on the above information, this variant is classified as benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000077995 SCV000691769 benign not specified no assertion criteria provided clinical testing
True Health Diagnostics RCV000130974 SCV000805208 likely benign Hereditary cancer-predisposing syndrome 2018-04-25 no assertion criteria provided clinical testing

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