rs4128941

Variant names:

• chr17-65535213-G-A
• rs4128941
• NM_004655.4:c.2237+413C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-65535213-G-A
• chr17-65535213-G-C
• chr17-65535213-G-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.2237+413C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0793 in 152,242 control chromosomes in the GnomAD database, including 701 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 0.079 (701 hom., cov: 33)
• Consequence: AXIN2 NM_004655.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 10 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: Ambry Genetics, ClinGen, 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXIN2	NM_004655.4	MANE Select	c.2237+413C>T		intron	N/A	NP_004646.3	Q9Y2T1
	AXIN2	NM_001363813.1		c.2042+413C>T		intron	N/A	NP_001350742.1	E7ES00

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXIN2	ENST00000307078.10	TSL:1 MANE Select	c.2237+413C>T		intron	N/A	ENSP00000302625.5	Q9Y2T1
	AXIN2	ENST00000375702.5	TSL:1	c.2042+413C>T		intron	N/A	ENSP00000364854.5	E7ES00
	AXIN2	ENST00000881031.1		c.2237+413C>T		intron	N/A	ENSP00000551090.1

Frequencies

GnomAD3 genomes AF: 0.0790 AC: 12025 AN: 152124 Hom.: 683 Cov.: 33

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.0591

Gnomad FIN AF: 0.0727

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0716

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

GnomAD4 genome AF: 0.0793 AC: 12078 AN: 152242 Hom.: 701 Cov.: 33 AF XY: 0.0843 AC XY: 6274 AN XY: 74416

African (AFR) AF: 0.100 AC: 4166 AN: 41534

American (AMR) AF: 0.142 AC: 2176 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 91 AN: 3470

East Asian (EAS) AF: 0.268 AC: 1388 AN: 5184

South Asian (SAS) AF: 0.0583 AC: 281 AN: 4822

European-Finnish (FIN) AF: 0.0727 AC: 771 AN: 10606

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0442 AC: 3007 AN: 68036

Other (OTH) AF: 0.0833 AC: 175 AN: 2102

Alfa AF: 0.0528 Hom.: 1516

Bravo AF: 0.0834

Asia WGS AF: 0.185 AC: 644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.76
PhyloP100		0.20
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: rs4128941; hg19: chr17-63531331;