17-65558251-C-G

Variant names:

• chr17-65558251-C-G
• NM_004655.4:c.370G>C

Variant summary

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

The NM_004655.4(AXIN2):​c.370G>C​(p.Asp124His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AXIN2 NM_004655.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.79

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN2	NM_004655.4	c.370G>C	p.Asp124His	missense_variant	Exon 2 of 11	ENST00000307078.10	NP_004646.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXIN2	ENST00000307078.10	c.370G>C	p.Asp124His	missense_variant	Exon 2 of 11	1	NM_004655.4	ENSP00000302625.5
ENSG00000266076	ENST00000577662.1	n.*546G>C		non_coding_transcript_exon_variant	Exon 4 of 7	2		ENSP00000462418.1
ENSG00000266076	ENST00000577662.1	n.*546G>C		3_prime_UTR_variant	Exon 4 of 7	2		ENSP00000462418.1

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	0.78
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	28
DANN	Benign	0.92
DEOGEN2	Benign	0.29	.;.;T;T;T;.;.;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.98	.;D;D;.;D;D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.77	T
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-4.7	D;.;.;D;.;.;.;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0010	D;.;.;D;.;.;.;D
Sift4G	Pathogenic	0.0010	D;D;D;D;.;.;.;.
Polyphen		1.0	.;.;D;D;.;.;.;.
Vest4		0.76
MutPred		0.37		Gain of MoRF binding (P = 0.0468);Gain of MoRF binding (P = 0.0468);Gain of MoRF binding (P = 0.0468);Gain of MoRF binding (P = 0.0468);Gain of MoRF binding (P = 0.0468);Gain of MoRF binding (P = 0.0468);Gain of MoRF binding (P = 0.0468);Gain of MoRF binding (P = 0.0468);
MVP		0.43
MPC		0.78
ClinPred		0.98	D
GERP RS		4.6
gMVP		0.71

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: chr17-63554369;