rs752373189

Positions:

• chr17-65558225-T-A
• chr17-65558225-T-C

Variant summary

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

The NM_004655.4(AXIN2):​c.396A>T​(p.Lys132Asn) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K132R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AXIN2 NM_004655.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.03

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	UniProt
AXIN2	NM_004655.4	c.396A>T	p.Lys132Asn	missense_variant	2/11	ENST00000307078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXIN2	ENST00000307078.10	c.396A>T	p.Lys132Asn	missense_variant	2/11	1	NM_004655.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Benign	0.97
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.50	D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.80	D
PROVEAN	Uncertain	-3.8	D;.;.;D;.;.;.;.
REVEL	Benign	0.19
Sift	Uncertain	0.0020	D;.;.;T;.;.;.;.
Sift4G	Benign	0.079	T;T;T;T;.;.;.;.
Polyphen		1.0	.;.;D;D;.;.;.;.
Vest4		0.75
MutPred		0.58		Loss of MoRF binding (P = 0.0437);Loss of MoRF binding (P = 0.0437);Loss of MoRF binding (P = 0.0437);Loss of MoRF binding (P = 0.0437);Loss of MoRF binding (P = 0.0437);Loss of MoRF binding (P = 0.0437);Loss of MoRF binding (P = 0.0437);Loss of MoRF binding (P = 0.0437);
MVP		0.53
MPC		0.78
ClinPred		0.99	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-63554343;