NM_004655.4:c.1166A>C

Variant names:

• chr17-65538237-T-G
• rs1060502142
• NM_004655.4:c.1166A>C

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>C​(p.His389Pro) 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.

• 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]

ENSG00000266076 (HGNC:):

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=0.19937688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN2	NM_004655.4	c.1166A>C	p.His389Pro	missense_variant	Exon 5 of 11	ENST00000307078.10	NP_004646.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXIN2	ENST00000307078.10	c.1166A>C	p.His389Pro	missense_variant	Exon 5 of 11	1	NM_004655.4	ENSP00000302625.5
ENSG00000266076	ENST00000577662.1	n.*1342A>C		non_coding_transcript_exon_variant	Exon 7 of 7	2		ENSP00000462418.1
ENSG00000266076	ENST00000577662.1	n.*1342A>C		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000462418.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250806 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135678

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

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	0.24
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.33	.;T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.033
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.90	.;D;.
M_CAP	Pathogenic	0.43	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.88	T
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.7	N;.;N
REVEL	Benign	0.23
Sift	Uncertain	0.014	D;.;D
Sift4G	Uncertain	0.035	D;D;D
Polyphen		0.0	.;B;B
Vest4		0.28
MutPred		0.17		Gain of glycosylation at H389 (P = 0.0264);Gain of glycosylation at H389 (P = 0.0264);Gain of glycosylation at H389 (P = 0.0264);
MVP		0.32
MPC		0.28
ClinPred		0.46	T
GERP RS		5.2
gMVP		0.19

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: rs1060502142; hg19: chr17-63534355;