rs1060502142

Positions:

• chr17-65538237-T-A
• chr17-65538237-T-C
• chr17-65538237-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004655.4(AXIN2):​c.1166A>T​(p.His389Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. H389Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: AXIN2 NM_004655.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.15

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26062024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXIN2	NM_004655.4	c.1166A>T	p.His389Leu	missense_variant	5/11	ENST00000307078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXIN2	ENST00000307078.10	c.1166A>T	p.His389Leu	missense_variant	5/11	1	NM_004655.4	P1
AXIN2	ENST00000375702.5	c.1166A>T	p.His389Leu	missense_variant	4/9	1
AXIN2	ENST00000618960.4	c.1166A>T	p.His389Leu	missense_variant	5/10	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.37	.;T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.0070
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	.;D;.
M_CAP	Pathogenic	0.40	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	0.58	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.9	D;.;D
REVEL	Benign	0.14
Sift	Uncertain	0.0050	D;.;D
Sift4G	Benign	0.095	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.47
MutPred		0.17		Loss of catalytic residue at L391 (P = 0.0994);Loss of catalytic residue at L391 (P = 0.0994);Loss of catalytic residue at L391 (P = 0.0994);
MVP		0.29
MPC		0.22
ClinPred		0.83	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.11

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: chr17-63534355;