ClinVar Miner

Submissions for variant NM_004655.4(AXIN2):c.2083G>T (p.Ala695Ser) (rs140510381)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000990052 SCV000559510 likely benign Oligodontia-colorectal cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000484417 SCV000568391 uncertain significance not provided 2018-07-09 criteria provided, single submitter clinical testing This variant is denoted AXIN2 c.2083G>T at the cDNA level, p.Ala695Ser (A695S) at the protein level, and results in the change of an Alanine to a Serine (GCT>TCT). This variant has been identified in at least three colorectal cancer patients (Khan 2011). AXIN2 Ala695Ser was observed at an allele frequency of 0.11% (34/30672) in individuals of South Asian ancestry in large population cohorts (Lek 2016). This variant is located within the exon 7 mutational hot spot (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 Ala695Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Mendelics RCV000990052 SCV001140816 benign Oligodontia-colorectal cancer syndrome 2019-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV001014371 SCV001175069 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-03 criteria provided, single submitter clinical testing Insufficient evidence
Center of Medical Genetics and Primary Health Care RCV001004836 SCV000987261 uncertain significance breast cancer 2020-04-08 no assertion criteria provided research This variant is in exon 6 in a non-functional domain. The allele frequency in GnomAD exomes is 0.000164 which is more than 0.0001 derived from the 1,065 clinically reported variants in gene AXIN2 (BS1 Benign Strong). This variant is also observed in healthy adults and GnomAD exomes allele count is 40 which is more than the threshold 5 for dominant gene AXIN2 (BS2 Benign Strong). Additionally, only 1 missense variant in AXIN2 gene is known to be pathogenic (BP1 Benign Supporting). In our study this variant was found in a 28-years-old female with unilateral breast cancer and no reported family history of cancer. Thus, we classified this variant as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.