ClinVar Miner

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

gnomAD frequency: 0.00583  dbSNP: rs72541809
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Total submissions: 27
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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 This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV003315717 SCV000252579 benign Familial adenomatous polyposis 1 2024-02-01 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000239214 SCV000297017 benign Familial multiple polyposis syndrome 2015-10-19 criteria provided, single submitter clinical testing
Illumina Laboratory Services, 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.
Genetic Services Laboratory, University of Chicago RCV000120034 SCV000593257 benign not specified 2020-02-07 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000128958 SCV000681499 benign Hereditary cancer-predisposing syndrome 2016-03-17 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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, part of Exact Sciences 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 RCV000586895 SCV001158623 benign not provided 2023-10-13 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000586895 SCV002497337 likely benign not provided 2024-04-01 criteria provided, single submitter clinical testing APC: BP4, BS1
Sema4, Sema4 RCV000128958 SCV002533519 benign Hereditary cancer-predisposing syndrome 2021-05-02 criteria provided, single submitter curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000120034 SCV002550594 likely benign not specified 2023-08-15 criteria provided, single submitter clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000128958 SCV002819236 benign Hereditary cancer-predisposing syndrome 2022-11-22 criteria provided, single submitter clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV003315717 SCV004015803 benign Familial adenomatous polyposis 1 2023-07-07 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV003315717 SCV004930997 benign Familial adenomatous polyposis 1 2024-03-08 criteria provided, single submitter clinical testing This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
ITMI RCV000120034 SCV000084166 not provided not specified 2013-09-19 no assertion provided reference population
Mayo Clinic Laboratories, Mayo Clinic RCV000120034 SCV000256937 benign not specified no assertion criteria provided research
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001353424 SCV000591102 benign Carcinoma of colon no assertion criteria provided clinical testing
True Health Diagnostics RCV000128958 SCV000693473 likely benign Hereditary cancer-predisposing syndrome 2017-11-10 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000586895 SCV001743869 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000120034 SCV001807219 benign not specified no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000120034 SCV001924079 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000120034 SCV001930372 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000586895 SCV001954221 likely benign not provided no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000586895 SCV002035368 likely benign not provided no assertion criteria provided clinical testing

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