chr17-65532005-G-A

Variant names:

• chr17-65532005-G-A
• rs7224837
• NM_004655.4:c.2406-1903C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004655.4(AXIN2):​c.2406-1903C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 152,064 control chromosomes in the GnomAD database, including 60,813 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 0.89 (60813 hom., cov: 30)
• Consequence: AXIN2 NM_004655.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 18 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004655.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXIN2	NM_004655.4	MANE Select	c.2406-1903C>T		intron	N/A	NP_004646.3
	AXIN2	NM_001363813.1		c.2211-1903C>T		intron	N/A	NP_001350742.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXIN2	ENST00000307078.10	TSL:1 MANE Select	c.2406-1903C>T		intron	N/A	ENSP00000302625.5
	AXIN2	ENST00000375702.5	TSL:1	c.2211-1903C>T		intron	N/A	ENSP00000364854.5
	AXIN2	ENST00000618960.4	TSL:5	c.2211-1903C>T		intron	N/A	ENSP00000478916.1

Frequencies

GnomAD3 genomes AF: 0.894 AC: 135865 AN: 151946 Hom.: 60761 Cov.: 30

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.891

Gnomad OTH AF: 0.913

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

GnomAD4 genome AF: 0.894 AC: 135977 AN: 152064 Hom.: 60813 Cov.: 30 AF XY: 0.896 AC XY: 66575 AN XY: 74318

African (AFR) AF: 0.894 AC: 37088 AN: 41488

American (AMR) AF: 0.894 AC: 13662 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 3299 AN: 3472

East Asian (EAS) AF: 0.818 AC: 4192 AN: 5124

South Asian (SAS) AF: 0.952 AC: 4579 AN: 4812

European-Finnish (FIN) AF: 0.906 AC: 9589 AN: 10584

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.891 AC: 60544 AN: 67984

Other (OTH) AF: 0.914 AC: 1927 AN: 2108

Alfa AF: 0.890 Hom.: 108228

Bravo AF: 0.892

Asia WGS AF: 0.875 AC: 3044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.51
DANN	Benign	0.79
PhyloP100		-1.5
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: rs7224837; hg19: chr17-63528123;