rs11079571

Variant names:

• chr17-65552563-A-G
• rs11079571
• NM_004655.4:c.816-2903T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 publications found

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]

AXIN2 Gene-Disease associations (from GenCC):

• oligodontia-cancer predisposition syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• tooth agenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• craniosynostosis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000266076 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AXIN2	NM_004655.4	c.816-2903T>C		intron_variant	Intron 2 of 10	ENST00000307078.10	NP_004646.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXIN2	ENST00000307078.10	c.816-2903T>C		intron_variant	Intron 2 of 10	1	NM_004655.4	ENSP00000302625.5
AXIN2	ENST00000375702.5	c.816-2903T>C		intron_variant	Intron 1 of 8	1		ENSP00000364854.5
ENSG00000266076	ENST00000577662.1	n.*992-2903T>C		intron_variant	Intron 4 of 6	2		ENSP00000462418.1
AXIN2	ENST00000618960.4	c.816-2903T>C		intron_variant	Intron 2 of 9	5		ENSP00000478916.1

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

African (AFR) AF: 0.617 AC: 25555 AN: 41432

American (AMR) AF: 0.795 AC: 12158 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2855 AN: 3472

East Asian (EAS) AF: 0.715 AC: 3688 AN: 5160

South Asian (SAS) AF: 0.787 AC: 3787 AN: 4810

European-Finnish (FIN) AF: 0.863 AC: 9156 AN: 10612

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 56004 AN: 67988

Other (OTH) AF: 0.750 AC: 1582 AN: 2110

Alfa AF: 0.799 Hom.: 45096

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
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11079571; hg19: chr17-63548681;