ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3732A>G (p.Gln1244=) (rs74380081)

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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 RCV000162515 SCV000212907 benign Hereditary cancer-predisposing syndrome 2014-08-14 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 RCV000757001 SCV000261927 benign Familial adenomatous polyposis 1 2020-12-08 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000260692 SCV000452008 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.
Color Health, Inc RCV000162515 SCV000681629 benign Hereditary cancer-predisposing syndrome 2016-03-18 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000500807 SCV000700377 benign not specified 2017-02-01 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000500807 SCV000805402 benign not specified 2017-01-30 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000500807 SCV000885021 benign not specified 2018-07-15 criteria provided, single submitter clinical testing
GeneDx RCV001711429 SCV001939929 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000500807 SCV000591154 benign not specified no assertion criteria provided clinical testing The APC p.Gln1244Gln 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 was identified in the dbSNP (ID: rs74380081) “with benign allele”, the ClinVar database (classified as “benign” by Ambry Genetics), the Clinvitae database (classified as a “variant of unknown significance by Emory Genetics), and the UMD (3X, classified as “likely neutral”). In the UMD database, the variant was identified with a co-occurring pathogenic APC variant (c.4666delA (p.Thr1556LeufsX9)), increasing the likelihood that the p.Gln1244Gln variant does not have clinical significance. In addition, the variant was identified in several populations at polymorphic allelic frequencies: 1000 Genomes Project (frequency: 0.014), the African population in the Exome Aggregation Consortium (ExAC) database (frequency: 0.038), and the African American cohort of the Exome Variant Server ESP Project (frequency: 0.036). The variant was not identified in the literature, nor was it identified in any of the following databases: InSiGHT Colon Cancer Gene Variant Database, “Zhejiang Colon Cancer Database”, GeneInsight COGR database, COSMIC. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict the creation of a potential cryptic 3’ (splice donor) site; however, this is not very predictive of pathogenicity. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000500807 SCV000691742 benign not specified no assertion criteria provided clinical testing
True Health Diagnostics RCV000162515 SCV000787835 likely benign Hereditary cancer-predisposing syndrome 2018-01-05 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000500807 SCV001808727 benign not specified no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000500807 SCV001925174 benign not specified no assertion criteria provided clinical testing

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