ClinVar Miner

Submissions for variant NM_004655.4(AXIN2):c.1363C>G (p.Pro455Ala)

gnomAD frequency: 0.00003  dbSNP: rs779863826
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000465208 SCV000548589 uncertain significance Oligodontia-cancer predisposition syndrome 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 455 of the AXIN2 protein (p.Pro455Ala). This variant is present in population databases (rs779863826, gnomAD 0.01%). 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: 408785). 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 expected to disrupt AXIN2 protein function with a positive 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 RCV000765389 SCV000896662 uncertain significance Oligodontia-cancer predisposition syndrome; Carcinoma of colon 2018-10-31 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000465208 SCV002526071 uncertain significance Oligodontia-cancer predisposition syndrome 2022-05-16 criteria provided, single submitter clinical testing The AXIN2 c.1363C>G (p.Pro455Ala) missense change has a maximum subpopulation frequency of 0.010% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). It is predicted to have a damaging effect on protein function (PP3), but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with oligodontia-cancer predisposition syndrome. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PP3.
Ambry Genetics RCV002379451 SCV002696035 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-06 criteria provided, single submitter clinical testing The c.1363C>G (p.P455A) alteration is located in exon 6 (coding exon 5) of the AXIN2 gene. This alteration results from a C to G substitution at nucleotide position 1363, causing the proline (P) at amino acid position 455 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV004568024 SCV005053223 uncertain significance Colorectal cancer 2023-11-30 criteria provided, single submitter clinical testing

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