17-65529344-G-GA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_004655.4(AXIN2):c.*631_*632insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 184,298 control chromosomes in the GnomAD database, including 95 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.027 (93 hom., cov: 32)
  • Exomes 𝑓: 0.16 (2 hom.)
• Consequence: AXIN2 NM_004655.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.16

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXIN2	NM_004655.4	c.*631_*632insT		3_prime_UTR_variant	11/11	ENST00000307078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXIN2	ENST00000307078.10	c.*631_*632insT		3_prime_UTR_variant	11/11	1	NM_004655.4	P1
AXIN2	ENST00000618960.4	c.*631_*632insT		3_prime_UTR_variant	10/10	5

Frequencies

GnomAD3 genomes AF: 0.0268 AC: 3835 AN: 143298 Hom.: 92 Cov.: 32

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.00870

Gnomad EAS AF: 0.0163

Gnomad SAS AF: 0.00731

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.00329

Gnomad NFE AF: 0.00840

Gnomad OTH AF: 0.0288

GnomAD4 exome AF: 0.165 AC: 6753 AN: 40946 Hom.: 2 Cov.: 0 AF XY: 0.162 AC XY: 3112 AN XY: 19184

Gnomad4 AFR exome AF: 0.242

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.0414

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.0268 AC: 3849 AN: 143352 Hom.: 93 Cov.: 32 AF XY: 0.0263 AC XY: 1829 AN XY: 69440

Gnomad4 AFR AF: 0.0705

Gnomad4 AMR AF: 0.0136

Gnomad4 ASJ AF: 0.00870

Gnomad4 EAS AF: 0.0163

Gnomad4 SAS AF: 0.00734

Gnomad4 FIN AF: 0.0161

Gnomad4 NFE AF: 0.00840

Gnomad4 OTH AF: 0.0281

Bravo AF: 0.0279

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Oligodontia-cancer predisposition syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs796431470; hg19: chr17-63525462;