ClinVar Miner

Submissions for variant NM_000038.6(APC):c.120G>A (p.Glu40=) (rs142720069)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001082954 SCV000166013 benign Familial adenomatous polyposis 1 2020-12-07 criteria provided, single submitter clinical testing
GeneDx RCV000201994 SCV000167017 benign not specified 2014-04-07 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 RCV000123674 SCV000213029 likely benign Hereditary cancer-predisposing syndrome 2014-09-18 criteria provided, single submitter clinical testing In silico models in agreement (benign);Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene;Synonymous alterations with insufficient evidence to classify as benign
Illumina Clinical Services Laboratory,Illumina RCV000340295 SCV000451981 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000201994 SCV000600038 likely benign not specified 2017-01-09 criteria provided, single submitter clinical testing
Color Health, Inc RCV000123674 SCV000681447 benign Hereditary cancer-predisposing syndrome 2016-03-09 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589882 SCV000693988 benign not provided 2016-05-02 criteria provided, single submitter clinical testing Variant summary: The APC c.120G>A variant affects a conserved nucleotide, resulting in synonymous amino acid change. This variant is found in 81/121234 control chromosomes at a frequency of 0.0006681, which is about 11 times greater than the estimated maximal expected frequency of a pathogenic allele (0.0000602) in this gene, suggesting this variant is benign. In addition, multiple clinical laboratories have classified this variant as benign/likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical laboratories. Taken together, this variant has been classified as Benign.
PreventionGenetics,PreventionGenetics RCV000201994 SCV000805364 benign not specified 2017-12-11 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589882 SCV000887501 benign not provided 2018-03-02 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001289734 SCV001477712 likely benign none provided 2020-04-01 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000201994 SCV000256909 likely benign not specified no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001082954 SCV001550237 likely benign Familial adenomatous polyposis 1 no assertion criteria provided clinical testing The APC p.Glu40= variant was identified in 4 of 3182 proband chromosomes (frequency: 0.0013) from individuals or families with FAP (Kerr 2013). The variant was also identified in dbSNP (ID: rs142720069) as "With other allele ", and in ClinVar database (classified as benign by Invitae, GeneDx, Color Genimics and two clinical laboratories; as likely benign by Ambry Genetics and three clinical laboratories). The variant was not identified in GeneInsight-COGR, Cosmic, LOVD 3.0, UMD-LSDB, or Zhejiang University, databases. The variant was identified in control databases in 194 of 276970 chromosomes at a frequency of 0.0007 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 128 of 24032 chromosomes (freq: 0.005), Other in 3 of 6454 chromosomes (freq: 0.0005), Latino in 19 of 34412 chromosomes (freq: 0.0006), European in 2 of 126492 chromosomes (freq: 0.00002), Ashkenazi Jewish in 42 of 10150 chromosomes (freq: 0.004), while the variant was not observed in the East Asian, Finnish, and South Asian populations. The p.Glu40= 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 occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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