17-65537661-G-C

Position:

• chr17-65537661-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004655.4(AXIN2):​c.1375C>G​(p.Arg459Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AXIN2 NM_004655.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.25

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]

ACMG classification

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	Protein	UniProt
AXIN2	NM_004655.4	c.1375C>G	p.Arg459Gly	missense_variant	6/11	ENST00000307078.10	NP_004646.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AXIN2	ENST00000307078.10	c.1375C>G	p.Arg459Gly	missense_variant	6/11	1	NM_004655.4	ENSP00000302625	P1
AXIN2	ENST00000375702.5	c.1375C>G	p.Arg459Gly	missense_variant	5/9	1		ENSP00000364854
AXIN2	ENST00000618960.4	c.1375C>G	p.Arg459Gly	missense_variant	6/10	5		ENSP00000478916

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 82

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	.;T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	.;D;.
M_CAP	Pathogenic	0.65	D
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Benign	-0.49	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.0	D;.;D
REVEL	Benign	0.28
Sift	Uncertain	0.027	D;.;D
Sift4G	Uncertain	0.055	T;T;T
Polyphen		0.55	.;P;P
Vest4		0.72
MutPred		0.61		Gain of glycosylation at S461 (P = 0.0591);Gain of glycosylation at S461 (P = 0.0591);Gain of glycosylation at S461 (P = 0.0591);
MVP		0.53
MPC		0.62
ClinPred		0.99	D
GERP RS		5.1
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs777680532; hg19: chr17-63533779;