ClinVar Miner

Submissions for variant NM_004655.4(AXIN2):c.1882C>T (p.Arg628Trp) (rs200201811)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159777 SCV000209799 uncertain significance not provided 2018-08-09 criteria provided, single submitter clinical testing This variant is denoted AXIN2 c.1882C>T at the cDNA level, p.Arg628Trp (R628W) at the protein level, and results in the change of an Arginine to a Tryptophan (CGG>TGG). This variant has not, to our knowledge, been published in the literature as a germline variant; however, it was reported as a somatic variant in a colorectal tumor (Giannakis 2016). AXIN2 Arg628Trp was observed at an allele frequency of 0.06% (16/25,764) in individuals of European (non-Finnish) ancestry in large population cohorts (Lek 2016). This variant is not located in a known functional domain. Protein-based in silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. In addition, multiple splicing models predict that this variant may create a cryptic splice site and lead to abnormal splicing. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. Based on currently available evidence, it is unclear whether AXIN2 Arg628Trp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV001084242 SCV000288679 likely benign Oligodontia-colorectal cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV001013513 SCV001174107 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-09 criteria provided, single submitter clinical testing Insufficient evidence
Illumina Clinical Services Laboratory,Illumina RCV001084242 SCV001283757 benign Oligodontia-colorectal cancer syndrome 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.

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