17-65529182-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004655.4(AXIN2):c.*794C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 234,160 control chromosomes in the GnomAD database, including 2,007 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1114 hom., cov: 32)
  • Exomes 𝑓: 0.13 (893 hom.)
• Consequence: AXIN2 NM_004655.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -8.90

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 17-65529182-G-T is Benign according to our data. Variant chr17-65529182-G-T is described in ClinVar as [Benign]. Clinvar id is 324633.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXIN2	NM_004655.4	c.*794C>A		3_prime_UTR_variant	11/11	ENST00000307078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXIN2	ENST00000307078.10	c.*794C>A		3_prime_UTR_variant	11/11	1	NM_004655.4	P1
AXIN2	ENST00000618960.4	c.*794C>A		3_prime_UTR_variant	10/10	5

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16180 AN: 152080 Hom.: 1116 Cov.: 32

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.0390

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0985

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.135 AC: 11047 AN: 81962 Hom.: 893 Cov.: 0 AF XY: 0.138 AC XY: 5239 AN XY: 37840

Gnomad4 AFR exome AF: 0.0429

Gnomad4 AMR exome AF: 0.0964

Gnomad4 ASJ exome AF: 0.275

Gnomad4 EAS exome AF: 0.0169

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.0867

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.106 AC: 16175 AN: 152198 Hom.: 1114 Cov.: 32 AF XY: 0.105 AC XY: 7845 AN XY: 74408

Gnomad4 AFR AF: 0.0411

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.0393

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0985

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.135

Alfa AF: 0.0886 Hom.: 186

Bravo AF: 0.105

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Oligodontia-cancer predisposition syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.031
Dann	Benign	0.67

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: rs10438779; hg19: chr17-63525300;