rs779029020
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004655.4(AXIN2):c.1502G>T(p.Gly501Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,390 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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. G501E) 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 -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AXIN2 | NM_004655.4 | c.1502G>T | p.Gly501Val | missense_variant | 6/11 | ENST00000307078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.1502G>T | p.Gly501Val | missense_variant | 6/11 | 1 | NM_004655.4 | P1 | |
AXIN2 | ENST00000375702.5 | c.1502G>T | p.Gly501Val | missense_variant | 5/9 | 1 | |||
AXIN2 | ENST00000618960.4 | c.1502G>T | p.Gly501Val | missense_variant | 6/10 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151842Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249864Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135332
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461548Hom.: 1 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 727094
GnomAD4 genome ? AF: 0.00000659 AC: 1AN: 151842Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74112
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 12, 2023 | The p.G501V variant (also known as c.1502G>T), located in coding exon 5 of the AXIN2 gene, results from a G to T substitution at nucleotide position 1502. The glycine at codon 501 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is not well 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. - |
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Oct 27, 2021 | - - |
Oligodontia-cancer predisposition syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 501 of the AXIN2 protein (p.Gly501Val). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 1020007). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 12, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at