ClinVar Miner

Submissions for variant NM_004655.4(AXIN2):c.2000G>A (p.Ser667Asn)

gnomAD frequency: 0.00001  dbSNP: rs878854724
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230145 SCV000288686 uncertain significance Oligodontia-cancer predisposition syndrome 2024-01-30 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 667 of the AXIN2 protein (p.Ser667Asn). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with AXIN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 240004). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt AXIN2 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV000765384 SCV000896657 uncertain significance Oligodontia-cancer predisposition syndrome; Carcinoma of colon 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV001014047 SCV001174706 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-30 criteria provided, single submitter clinical testing The p.S667N variant (also known as c.2000G>A), located in coding exon 7 of the AXIN2 gene, results from a G to A substitution at nucleotide position 2000. The serine at codon 667 is replaced by asparagine, an amino acid with highly similar properties. This alteration was identified in 1/1358 non-cancer control individuals and in 0/57 cases, in a study looking at cancer predisposition mutations in patients with cutaneous melanoma and a history of at least two additional non-cutaneous melanoma primary cancers (Pritchard AL et al. PLoS One, 2018 Apr;13:e0194098). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001551935 SCV001772542 uncertain significance not provided 2019-04-15 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge
Baylor Genetics RCV003475824 SCV004213042 uncertain significance Colorectal cancer 2023-09-01 criteria provided, single submitter clinical testing

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