rs565565172
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004655.4(AXIN2):c.2108G>A(p.Arg703Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,936 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. R703G) has been classified as Uncertain significance.
Frequency
Consequence
NM_004655.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AXIN2 | NM_004655.4 | c.2108G>A | p.Arg703Lys | missense_variant | 8/11 | ENST00000307078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.2108G>A | p.Arg703Lys | missense_variant | 8/11 | 1 | NM_004655.4 | P1 | |
AXIN2 | ENST00000375702.5 | c.1913G>A | p.Arg638Lys | missense_variant | 6/9 | 1 | |||
AXIN2 | ENST00000618960.4 | c.1913G>A | p.Arg638Lys | missense_variant | 7/10 | 5 | |||
AXIN2 | ENST00000578251.1 | n.330G>A | non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152246Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000413 AC: 1AN: 242196Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 131618
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1460936Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726730
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Oligodontia-cancer predisposition syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 23, 2018 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with AXIN2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with lysine at codon 703 of the AXIN2 protein (p.Arg703Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2021 | The p.R703K variant (also known as c.2108G>A), located in coding exon 7 of the AXIN2 gene, results from a G to A substitution at nucleotide position 2108. The arginine at codon 703 is replaced by lysine, an amino acid with highly 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