rs151247101
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_004655.4(AXIN2):c.917C>T(p.Ala306Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,611,068 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A306G) has been classified as Uncertain significance.
Frequency
Consequence
NM_004655.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AXIN2 | NM_004655.4 | c.917C>T | p.Ala306Val | missense_variant | 3/11 | ENST00000307078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.917C>T | p.Ala306Val | missense_variant | 3/11 | 1 | NM_004655.4 | P1 | |
AXIN2 | ENST00000375702.5 | c.917C>T | p.Ala306Val | missense_variant | 2/9 | 1 | |||
AXIN2 | ENST00000618960.4 | c.917C>T | p.Ala306Val | missense_variant | 3/10 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000245 AC: 6AN: 245056Hom.: 0 AF XY: 0.0000302 AC XY: 4AN XY: 132366
GnomAD4 exome AF: 0.00000754 AC: 11AN: 1458734Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 725354
GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152334Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74500
ClinVar
Submissions by phenotype
Oligodontia-cancer predisposition syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 306 of the AXIN2 protein (p.Ala306Val). This variant is present in population databases (rs151247101, 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: 240040). 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. - |
Colorectal cancer Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 24, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 20, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 05, 2023 | The p.A306V variant (also known as c.917C>T), located in coding exon 2 of the AXIN2 gene, results from a C to T substitution at nucleotide position 917. The alanine at codon 306 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at