17-65529182-G-T

Variant names:

• chr17-65529182-G-T
• rs10438779
• NM_004655.4:c.*794C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -8.90
• Publications: 4 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

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 324633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 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.*794C>A		3_prime_UTR	Exon 11 of 11	NP_004646.3	Q9Y2T1
	AXIN2	NM_001363813.1		c.*794C>A		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.*794C>A		3_prime_UTR	Exon 11 of 11	ENSP00000302625.5	Q9Y2T1
	AXIN2	ENST00000881031.1		c.*794C>A		3_prime_UTR	Exon 11 of 11	ENSP00000551090.1
	AXIN2	ENST00000881032.1		c.*794C>A		3_prime_UTR	Exon 11 of 11	ENSP00000551091.1

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

African (AFR) AF: 0.0429 AC: 167 AN: 3896

American (AMR) AF: 0.0964 AC: 249 AN: 2582

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 1413 AN: 5132

East Asian (EAS) AF: 0.0169 AC: 193 AN: 11432

South Asian (SAS) AF: 0.131 AC: 96 AN: 734

European-Finnish (FIN) AF: 0.0867 AC: 13 AN: 150

Middle Eastern (MID) AF: 0.209 AC: 103 AN: 492

European-Non Finnish (NFE) AF: 0.154 AC: 7822 AN: 50756

Other (OTH) AF: 0.146 AC: 991 AN: 6788

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

African (AFR) AF: 0.0411 AC: 1707 AN: 41542

American (AMR) AF: 0.103 AC: 1568 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 978 AN: 3470

East Asian (EAS) AF: 0.0393 AC: 204 AN: 5196

South Asian (SAS) AF: 0.131 AC: 630 AN: 4814

European-Finnish (FIN) AF: 0.0985 AC: 1043 AN: 10588

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9604 AN: 67984

Other (OTH) AF: 0.135 AC: 286 AN: 2114

Alfa AF: 0.0878 Hom.: 187

Bravo AF: 0.105

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Oligodontia-cancer predisposition syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.031
DANN	Benign	0.67
PhyloP100		-8.9
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: rs10438779; hg19: chr17-63525300;