rs1060502128
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_004655.4(AXIN2):āc.1564C>Gā(p.His522Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H522P) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AXIN2 | NM_004655.4 | c.1564C>G | p.His522Asp | missense_variant | 6/11 | ENST00000307078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.1564C>G | p.His522Asp | missense_variant | 6/11 | 1 | NM_004655.4 | P1 | |
AXIN2 | ENST00000375702.5 | c.1564C>G | p.His522Asp | missense_variant | 5/9 | 1 | |||
AXIN2 | ENST00000618960.4 | c.1564C>G | p.His522Asp | missense_variant | 6/10 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461868Hom.: 0 Cov.: 35 AF XY: 0.00000688 AC XY: 5AN XY: 727242
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Oligodontia-cancer predisposition syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 2023 | This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 522 of the AXIN2 protein (p.His522Asp). 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: 408765). 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. 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 | Feb 27, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 17, 2020 | Not observed in large population cohorts (Lek 2016); 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 30, 2023 | The p.H522D variant (also known as c.1564C>G), located in coding exon 5 of the AXIN2 gene, results from a C to G substitution at nucleotide position 1564. The histidine at codon 522 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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