17-65530031-G-C

Variant names:

• chr17-65530031-G-C
• NM_004655.4:c.2477C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004655.4(AXIN2):​c.2477C>G​(p.Thr826Arg) 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. 12/19 in silico tools predict 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: 33)
• Consequence: AXIN2 NM_004655.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.89

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.307783).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN2	NM_004655.4	c.2477C>G	p.Thr826Arg	missense_variant	Exon 11 of 11	ENST00000307078.10	NP_004646.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXIN2	ENST00000307078.10	c.2477C>G	p.Thr826Arg	missense_variant	Exon 11 of 11	1	NM_004655.4	ENSP00000302625.5
AXIN2	ENST00000375702.5	c.2282C>G	p.Thr761Arg	missense_variant	Exon 9 of 9	1		ENSP00000364854.5
AXIN2	ENST00000618960.4	c.2282C>G	p.Thr761Arg	missense_variant	Exon 10 of 10	5		ENSP00000478916.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	.;T;T
Eigen	Benign	0.060
Eigen_PC	Benign	0.051
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	.;D;.
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.84	T
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.9	N;.;N
REVEL	Benign	0.19
Sift	Uncertain	0.0050	D;.;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		0.54	.;P;P
Vest4		0.36
MutPred		0.57		Gain of solvent accessibility (P = 0.024);.;.;
MVP		0.50
MPC		0.42
ClinPred		0.87	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.61

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: chr17-63526149;