17-65549565-C-G

Position:

• chr17-65549565-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000307078.10(AXIN2):​c.911G>C​(p.Ser304Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. S304G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AXIN2 ENST00000307078.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.86

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.838

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AXIN2	NM_004655.4	c.911G>C	p.Ser304Thr	missense_variant	3/11	ENST00000307078.10	NP_004646.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AXIN2	ENST00000307078.10	c.911G>C	p.Ser304Thr	missense_variant	3/11	1	NM_004655.4	ENSP00000302625	P1
AXIN2	ENST00000375702.5	c.911G>C	p.Ser304Thr	missense_variant	2/9	1		ENSP00000364854
AXIN2	ENST00000618960.4	c.911G>C	p.Ser304Thr	missense_variant	3/10	5		ENSP00000478916

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	.;T;T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	.;D;.
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Uncertain	0.59	D
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.6	D;.;D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0030	D;.;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.81
MutPred		0.36		Gain of glycosylation at S304 (P = 0.0441);Gain of glycosylation at S304 (P = 0.0441);Gain of glycosylation at S304 (P = 0.0441);
MVP		0.67
MPC		0.68
ClinPred		0.98	D
GERP RS		5.9
gMVP		0.58

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: chr17-63545683;