chr17-65558487-A-ACCTGGC
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4BS2
The NM_004655.4(AXIN2):c.133_134insGCCAGG(p.Gly43_Gln44dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000754 in 1,458,674 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. V45V) has been classified as Likely benign.
Frequency
Consequence
NM_004655.4 inframe_insertion
Scores
Clinical Significance
Conservation
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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.133_134insGCCAGG | p.Gly43_Gln44dup | inframe_insertion | 2/11 | ENST00000307078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.133_134insGCCAGG | p.Gly43_Gln44dup | inframe_insertion | 2/11 | 1 | NM_004655.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000241 AC: 6AN: 249070Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134578
GnomAD4 exome AF: 0.00000754 AC: 11AN: 1458674Hom.: 0 Cov.: 33 AF XY: 0.00000827 AC XY: 6AN XY: 725248
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Oligodontia-cancer predisposition syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 01, 2023 | This variant, c.128_133dup, results in the insertion of 2 amino acid(s) of the AXIN2 protein (p.Gly43_Gln44dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs772061457, gnomAD 0.03%). 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: 464532). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 | Mar 24, 2024 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 21, 2022 | The c.128_133dupGCCAGG variant (also known as p.G43_Q44dup) is located in coding exon 1 of the AXIN2 gene. This variant results from an in-frame duplication of 6 nucleotides at positions 128 to 133. This results in the duplication of 2 extra residues (GQ) between codons 43 and 44. This amino acid region is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). 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