17-65545379-T-C

Position:

• chr17-65545379-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004655.4(AXIN2):​c.957-3822A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,108 control chromosomes in the GnomAD database, including 25,906 homozygotes. 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: 𝑓 0.55 (25906 hom., cov: 32)
• Consequence: AXIN2 NM_004655.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AXIN2	NM_004655.4	c.957-3822A>G		intron_variant		ENST00000307078.10	NP_004646.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AXIN2	ENST00000307078.10	c.957-3822A>G		intron_variant		1	NM_004655.4	ENSP00000302625	P1
AXIN2	ENST00000375702.5	c.957-3822A>G		intron_variant		1		ENSP00000364854
AXIN2	ENST00000618960.4	c.957-3822A>G		intron_variant		5		ENSP00000478916

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83692 AN: 151988 Hom.: 25910 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.572

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.550 AC: 83690 AN: 152108 Hom.: 25906 Cov.: 32 AF XY: 0.549 AC XY: 40841 AN XY: 74344

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.750

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.677

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.565

Alfa AF: 0.671 Hom.: 68519

Bravo AF: 0.533

Asia WGS AF: 0.447 AC: 1557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	16
DANN	Benign	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

LitVar

Other links and lift over

dbSNP: rs4791171; hg19: chr17-63541497;