Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001229846 | SCV001402305 | uncertain significance | Oligodontia-cancer predisposition syndrome | 2024-04-15 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 10 of the AXIN2 gene. It does not directly change the encoded amino acid sequence of the AXIN2 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). 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: 956948). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. |
Ambry Genetics | RCV002451541 | SCV002738557 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-18 | criteria provided, single submitter | clinical testing | The c.2405+3A>G intronic variant results from an A to G substitution 3 nucleotides after coding exon 9 in the AXIN2 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004998749 | SCV005624986 | uncertain significance | not provided | 2024-03-13 | criteria provided, single submitter | clinical testing | The AXIN2 c.2405+3A>G variant has not been reported in individuals with AXIN2-related conditions in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on AXIN2 mRNA splicing yielded inconclusive findings. Based on the available information, we are unable to determine the clinical significance of this variant. |