Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000640202 | SCV000761791 | pathogenic | Oligodontia-cancer predisposition syndrome | 2022-09-01 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with AXIN2-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 533178). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Phe770Serfs*12) in the AXIN2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AXIN2 are known to be pathogenic (PMID: 15042511, 21416598). |
| Ambry Genetics | RCV001015156 | SCV001175961 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-06-20 | criteria provided, single submitter | clinical testing | The c.2309delT variant, located in coding exon 9 of the AXIN2 gene, results from a deletion of one nucleotide at nucleotide position 2309, causing a translational frameshift with a predicted alternate stop codon (p.F770Sfs*12). Based on internal structural assessment, this alteration eliminates most of the DIX domain, which is critical for formation of the Wnt signaling complex (Fiedler M et al. Proc. Natl. Acad. Sci. U.S.A. 2011 Feb;108(5):1937-42). This alteration is expected to result in loss of function by premature protein truncation. This alteration has been observed in at least one individual with a personal and/or family history that is consistent with AXIN2-related disease (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |