17-65545379-T-C

Variant names:

• chr17-65545379-T-C
• rs4791171
• NM_004655.4:c.957-3822A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 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.957-3822A>G		intron	N/A	NP_004646.3
	AXIN2	NM_001363813.1		c.957-3822A>G		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.957-3822A>G		intron	N/A	ENSP00000302625.5
	AXIN2	ENST00000375702.5	TSL:1	c.957-3822A>G		intron	N/A	ENSP00000364854.5
	ENSG00000266076	ENST00000577662.1	TSL:2	n.*1133-3822A>G		intron	N/A	ENSP00000462418.1

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

African (AFR) AF: 0.260 AC: 10784 AN: 41492

American (AMR) AF: 0.580 AC: 8861 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2603 AN: 3472

East Asian (EAS) AF: 0.359 AC: 1858 AN: 5172

South Asian (SAS) AF: 0.619 AC: 2983 AN: 4818

European-Finnish (FIN) AF: 0.677 AC: 7165 AN: 10576

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47349 AN: 67996

Other (OTH) AF: 0.565 AC: 1186 AN: 2100

Alfa AF: 0.646 Hom.: 100506

Bravo AF: 0.533

Asia WGS AF: 0.447 AC: 1557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	16
DANN	Benign	0.61
PhyloP100		1.5
Mutation Taster		=99/1	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: rs4791171; hg19: chr17-63541497;