chr17-65529488-CACTCCTAGCTCA-C

Variant names:

• chr17-65529488-CACTCCTAGCTCA-C
• rs548756747
• NM_004655.4:c.*476_*487delTGAGCTAGGAGT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004655.4(AXIN2):​c.*476_*487delTGAGCTAGGAGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00447 in 289,820 control chromosomes in the GnomAD database, including 8 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (4 hom.)
• Consequence: AXIN2 NM_004655.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.56
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 17-65529488-CACTCCTAGCTCA-C is Benign according to our data. Variant chr17-65529488-CACTCCTAGCTCA-C is described in ClinVar as Benign. ClinVar VariationId is 2648106.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00439 (669/152316) while in subpopulation SAS AF = 0.00559 (27/4826). AF 95% confidence interval is 0.00467. There are 4 homozygotes in GnomAd4. There are 340 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 669 AD gene.

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.*476_*487delTGAGCTAGGAGT		3_prime_UTR	Exon 11 of 11	NP_004646.3	Q9Y2T1
	AXIN2	NM_001363813.1		c.*476_*487delTGAGCTAGGAGT		3_prime_UTR	Exon 10 of 10	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.*476_*487delTGAGCTAGGAGT		3_prime_UTR	Exon 11 of 11	ENSP00000302625.5	Q9Y2T1
	AXIN2	ENST00000881031.1		c.*476_*487delTGAGCTAGGAGT		3_prime_UTR	Exon 11 of 11	ENSP00000551090.1
	AXIN2	ENST00000881032.1		c.*476_*487delTGAGCTAGGAGT		3_prime_UTR	Exon 11 of 11	ENSP00000551091.1

Frequencies

GnomAD3 genomes AF: 0.00440 AC: 669 AN: 152198 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00425

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00511

Gnomad OTH AF: 0.00960

GnomAD4 exome AF: 0.00455 AC: 626 AN: 137504 Hom.: 4 AF XY: 0.00427 AC XY: 285 AN XY: 66734

African (AFR) AF: 0.00136 AC: 7 AN: 5150

American (AMR) AF: 0.00523 AC: 32 AN: 6120

Ashkenazi Jewish (ASJ) AF: 0.00443 AC: 28 AN: 6324

East Asian (EAS) AF: 0.00 AC: 0 AN: 14488

South Asian (SAS) AF: 0.00515 AC: 42 AN: 8154

European-Finnish (FIN) AF: 0.00967 AC: 26 AN: 2690

Middle Eastern (MID) AF: 0.00893 AC: 6 AN: 672

European-Non Finnish (NFE) AF: 0.00503 AC: 424 AN: 84238

Other (OTH) AF: 0.00631 AC: 61 AN: 9668

GnomAD4 genome AF: 0.00439 AC: 669 AN: 152316 Hom.: 4 Cov.: 32 AF XY: 0.00456 AC XY: 340 AN XY: 74482

African (AFR) AF: 0.00118 AC: 49 AN: 41576

American (AMR) AF: 0.00425 AC: 65 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4826

European-Finnish (FIN) AF: 0.0123 AC: 131 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00512 AC: 348 AN: 68030

Other (OTH) AF: 0.00950 AC: 20 AN: 2106

Alfa AF: 0.00416 Hom.: 0

Bravo AF: 0.00382

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs548756747; hg19: chr17-63525606; COSMIC: COSV61061314; COSMIC: COSV61061314;