ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1695A>G (p.Glu565=) (rs77921116)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162514 SCV000212906 benign Hereditary cancer-predisposing syndrome 2014-11-19 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
Invitae RCV000757000 SCV000261926 benign Familial adenomatous polyposis 1 2020-12-08 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000259790 SCV000451991 benign APC-Associated Polyposis Disorders 2018-01-13 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.
Color Health, Inc RCV000162514 SCV000681485 benign Hereditary cancer-predisposing syndrome 2016-03-18 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000202246 SCV000700376 benign not specified 2017-02-01 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000202246 SCV000805372 benign not specified 2017-01-30 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000202246 SCV000885020 benign not specified 2018-07-15 criteria provided, single submitter clinical testing
GeneDx RCV001711321 SCV001943945 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000202246 SCV000256931 benign not specified no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000202246 SCV000591085 benign not specified no assertion criteria provided clinical testing The APC p.Glu565Glu variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant is listed in UMD (3X) as a neutral variant (co-occurring with a pathogenic APC variant in one sample), in the ClinVar database (classified as benign by Ambry Genetics), and in the Invitae database (classified as “variant of unknown significance” by Emory Genetics). Three of five in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict the potential creation of a 5’ splice site; however, this information is not predictive enough to assume pathogenicity. The variant was identified in the literature in 10 of 1695 familial adenomatous polyposis cases (allelic frequency: 0.003); the authors suggest the variant is likely benign due to a co-occurring pathogenic APC variant identified in at least one of these individuals (Kerr 2013). In addition, the variant was identified in several populations at polymorphic allelic frequencies: 1000 Genomes Project (frequency: 0.014), Exome Variant Server ESP project (African American cohort frequency: 0.036, and the ExAC browser (African cohort frequency: 0.038). In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
True Health Diagnostics RCV000162514 SCV000787831 likely benign Hereditary cancer-predisposing syndrome 2018-01-05 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000202246 SCV001808178 benign not specified no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000202246 SCV001920722 benign not specified no assertion criteria provided clinical testing

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