chr17-65537822-T-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004655.4(AXIN2):āc.1214A>Gā(p.Glu405Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E405A) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
AXIN2
NM_004655.4 missense
NM_004655.4 missense
Scores
2
8
6
Clinical Significance
Conservation
PhyloP100: 6.95
Genes affected
AXIN2 (HGNC:904): (axin 2) The Axin-related protein, Axin2, presumably plays an important role in the regulation of the stability of beta-catenin in the Wnt signaling pathway, like its rodent homologs, mouse conductin/rat axil. In mouse, conductin organizes a multiprotein complex of APC (adenomatous polyposis of the colon), beta-catenin, glycogen synthase kinase 3-beta, and conductin, which leads to the degradation of beta-catenin. Apparently, the deregulation of beta-catenin is an important event in the genesis of a number of malignancies. The AXIN2 gene has been mapped to 17q23-q24, a region that shows frequent loss of heterozygosity in breast cancer, neuroblastoma, and other tumors. Mutations in this gene have been associated with colorectal cancer with defective mismatch repair. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AXIN2 | NM_004655.4 | c.1214A>G | p.Glu405Gly | missense_variant | 6/11 | ENST00000307078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.1214A>G | p.Glu405Gly | missense_variant | 6/11 | 1 | NM_004655.4 | P1 | |
AXIN2 | ENST00000375702.5 | c.1214A>G | p.Glu405Gly | missense_variant | 5/9 | 1 | |||
AXIN2 | ENST00000618960.4 | c.1214A>G | p.Glu405Gly | missense_variant | 6/10 | 5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1408220Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 694610
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1408220
Hom.:
Cov.:
36
AF XY:
AC XY:
0
AN XY:
694610
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 01, 2023 | The p.E405G variant (also known as c.1214A>G), located in coding exon 5 of the AXIN2 gene, results from an A to G substitution at nucleotide position 1214. The glutamic acid at codon 405 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D
REVEL
Uncertain
Sift
Uncertain
D;.;T
Sift4G
Uncertain
D;D;D
Polyphen
0.32
.;B;B
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.0522);Gain of relative solvent accessibility (P = 0.0522);Gain of relative solvent accessibility (P = 0.0522);
MVP
MPC
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.