ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6525A>G (p.Thr2175=) (rs200151646)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000119189 SCV000153926 benign Familial adenomatous polyposis 1 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000254629 SCV000209478 likely benign not specified 2018-03-14 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 RCV000159521 SCV000214464 likely benign Hereditary cancer-predisposing syndrome 2015-01-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000374754 SCV000452036 uncertain significance 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000254629 SCV000600129 uncertain significance not specified 2016-07-05 criteria provided, single submitter clinical testing
Color RCV000159521 SCV000681805 likely benign Hereditary cancer-predisposing syndrome 2016-09-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000254629 SCV000918460 benign not specified 2017-10-31 criteria provided, single submitter clinical testing Variant Summary: The c.6525A>G (p.Thr2175Thr) variant involves the alteration of a non-conserved nucleotide resulting in a synonymous change. 4/5 in silico tools via Alamut predict the strengthening of a cryptic splice donor site as well as minor changes to other binding motifs, however, the significance of these predictions has not been supported with functional studies. The variant was observed in the general population dataset of gnomAD at an allele frequency of 0.00011 (32/275542 chromosomes tested), predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0002 (26/126026 chromosomes). This frequency exceeds the maximal expected allele frequency for a pathogenic variant in APC (0.00007) by 3-folds, strongly supporting that this is a benign polymorphism found primarily in population(s) of European origin. The variant has been reported once in the literature in a CRC patient without strong evidence for or against pathogenicity (Borras_2013). In addition, multiple clinical laboratories/reputable databases have classified the variant as likely benign. Taken together, this variant has been classified as benign.

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