chr17-65537739-C-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_004655.4(AXIN2):āc.1297G>Cā(p.Glu433Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000446 in 1,567,802 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E433D) 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.1297G>C | p.Glu433Gln | missense_variant | 6/11 | ENST00000307078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.1297G>C | p.Glu433Gln | missense_variant | 6/11 | 1 | NM_004655.4 | P1 | |
AXIN2 | ENST00000375702.5 | c.1297G>C | p.Glu433Gln | missense_variant | 5/9 | 1 | |||
AXIN2 | ENST00000618960.4 | c.1297G>C | p.Glu433Gln | missense_variant | 6/10 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151982Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000573 AC: 1AN: 174428Hom.: 0 AF XY: 0.0000107 AC XY: 1AN XY: 93240
GnomAD4 exome AF: 0.00000424 AC: 6AN: 1415820Hom.: 0 Cov.: 37 AF XY: 0.00000571 AC XY: 4AN XY: 700046
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151982Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74216
ClinVar
Submissions by phenotype
Oligodontia-cancer predisposition syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 27, 2023 | 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on AXIN2 protein function. This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 433 of the AXIN2 protein (p.Glu433Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 464535). 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 31, 2022 | The p.E433Q variant (also known as c.1297G>C), located in coding exon 5 of the AXIN2 gene, results from a G to C substitution at nucleotide position 1297. The glutamic acid at codon 433 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. 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