rs372987093
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_004655.4(AXIN2):c.1291T>A(p.Tyr431Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000102 in 1,571,994 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/19 in silico tools predict a benign outcome for this variant. 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. Y431C) has been classified as Uncertain significance.
Frequency
Consequence
NM_004655.4 missense
Scores
Clinical Significance
Conservation
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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.1291T>A | p.Tyr431Asn | missense_variant | 6/11 | ENST00000307078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.1291T>A | p.Tyr431Asn | missense_variant | 6/11 | 1 | NM_004655.4 | P1 | |
AXIN2 | ENST00000375702.5 | c.1291T>A | p.Tyr431Asn | missense_variant | 5/9 | 1 | |||
AXIN2 | ENST00000618960.4 | c.1291T>A | p.Tyr431Asn | missense_variant | 6/10 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151928Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000106 AC: 15AN: 1420066Hom.: 0 Cov.: 37 AF XY: 0.0000142 AC XY: 10AN XY: 702598
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151928Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74182
ClinVar
Submissions by phenotype
Oligodontia-cancer predisposition syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | This sequence change replaces tyrosine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 431 of the AXIN2 protein (p.Tyr431Asn). 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: 464534). 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 | Mar 22, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 16, 2023 | The p.Y431N variant (also known as c.1291T>A), located in coding exon 5 of the AXIN2 gene, results from a T to A substitution at nucleotide position 1291. The tyrosine at codon 431 is replaced by asparagine, an amino acid with dissimilar properties. This amino acid position is not well 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at