rs11079571

chr17-65552563-A-G

Variant summary

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

The NM_004655.4(AXIN2):c.816-2903T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,080 control chromosomes in the GnomAD database, including 44,732 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 0.76 (44732 hom., cov: 31)
• Consequence: AXIN2 NM_004655.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.45

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXIN2	NM_004655.4	c.816-2903T>C		intron_variant		ENST00000307078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXIN2	ENST00000307078.10	c.816-2903T>C		intron_variant		1	NM_004655.4	P1
AXIN2	ENST00000375702.5	c.816-2903T>C		intron_variant		1
AXIN2	ENST00000618960.4	c.816-2903T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115667 AN: 151962 Hom.: 44694 Cov.: 31

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.761 AC: 115758 AN: 152080 Hom.: 44732 Cov.: 31 AF XY: 0.765 AC XY: 56884 AN XY: 74338

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.822

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.787

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.750

Alfa AF: 0.800 Hom.: 35896

Bravo AF: 0.752

Asia WGS AF: 0.745 AC: 2592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.15
Dann	Benign	0.34

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: rs11079571; hg19: chr17-63548681;