ClinVar Miner

Submissions for variant NM_004655.4(AXIN2):c.1168A>G (p.Ser390Gly) (rs139871607)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000656767 SCV000149775 uncertain significance not provided 2018-03-13 criteria provided, single submitter clinical testing This variant is denoted AXIN2 c.1168A>G at the cDNA level, p.Ser390Gly (S390G) at the protein level, and results in the change of a Serine to a Glycine (AGC>GGC). This variant has been observed in an individual with early-onset colorectal cancer whose tumor studies demonstrated microsatellite instability and absence of MSH2/MSH6 protein expression on immunohistochemistry, without a detectable mismatch repair variant in the germline or tumor (Jansen 2016). AXIN2 Ser390Gly was observed at an allele frequency of 0.14% (183/126,294) in individuals of European ancestry in large population cohorts (Lek 2016). This variant is located in the GSK3-beta binding domain (Salahshor 2005). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether AXIN2 Ser390Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000227795 SCV000288645 likely benign Oligodontia-colorectal cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000227795 SCV000405709 benign Oligodontia-colorectal cancer syndrome 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000227795 SCV000788238 likely benign Oligodontia-colorectal cancer syndrome 2018-04-01 criteria provided, single submitter research The AXIN2 variant designated as NM_004655.3:c.1168A>G (p.Ser390Gly) is classified as likely benign. This variant has been reported in several population databases. It is present in approximately 1 in 350 individuals with European ancestry ( This population frequency is much higher than other pathogenic variants in AXIN2 and not consistent with the reported oligodontia-cancer syndrome frequency. This variant has been reported as likely benign by other laboratories (ClinVar Variation ID: 127934). Bayesian analysis integrating all of this data (Tavtigian et al, 2018, PMID:29300386) gives less than 1% probability of pathogenicity, which is consistent with a classification of likely benign. This variant is not predicted to alter AXIN2 function or modify cancer risk. A modest (less than 2 fold) increase in cancer risk due to this variant cannot be excluded. This analysis was performed in conjunction with the family studies project as part of the University of Washington Find My Variant Study.
Ambry Genetics RCV001010110 SCV001170258 likely benign Hereditary cancer-predisposing syndrome 2018-12-26 criteria provided, single submitter clinical testing Other strong data supporting benign classification
CSER _CC_NCGL, University of Washington RCV000417356 SCV000503528 uncertain significance Oligodontia; Colorectal cancer 2016-08-01 no assertion criteria provided research Found in patient having exome sequencing due to suspicion for hereditary colon cancer and/or polyps. Patient is a 59 year old with a history of over 50 colon polyps.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000115866 SCV000691790 uncertain significance not specified no assertion criteria provided clinical testing

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