rs1244431726
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_004655.4(AXIN2):c.2104C>T(p.Arg702Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,292 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R702H) 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AXIN2 | NM_004655.4 | c.2104C>T | p.Arg702Cys | missense_variant | 8/11 | ENST00000307078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.2104C>T | p.Arg702Cys | missense_variant | 8/11 | 1 | NM_004655.4 | P1 | |
AXIN2 | ENST00000375702.5 | c.1909C>T | p.Arg637Cys | missense_variant | 6/9 | 1 | |||
AXIN2 | ENST00000618960.4 | c.1909C>T | p.Arg637Cys | missense_variant | 7/10 | 5 | |||
AXIN2 | ENST00000578251.1 | n.326C>T | non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000412 AC: 1AN: 242686Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 131838
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461064Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 726784
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152228Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
Oligodontia-cancer predisposition syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 09, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 702 of the AXIN2 protein (p.Arg702Cys). 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. 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. ClinVar contains an entry for this variant (Variation ID: 938759). This variant has not been reported in the literature in individuals affected with AXIN2-related conditions. 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 01, 2023 | The p.R702C variant (also known as c.2104C>T), located in coding exon 7 of the AXIN2 gene, results from a C to T substitution at nucleotide position 2104. The arginine at codon 702 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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