rs10438779

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-65529182-G-A
• chr17-65529182-G-C
• chr17-65529182-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004655.4(AXIN2):​c.*794C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 234,092 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: AXIN2 NM_004655.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000138 (21/152108) while in subpopulation AMR AF = 0.000851 (13/15268). AF 95% confidence interval is 0.000503. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 21 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.*794C>T		3_prime_UTR	Exon 11 of 11	NP_004646.3	Q9Y2T1
	AXIN2	NM_001363813.1		c.*794C>T		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>T		3_prime_UTR	Exon 11 of 11	ENSP00000302625.5	Q9Y2T1
	AXIN2	ENST00000881031.1		c.*794C>T		3_prime_UTR	Exon 11 of 11	ENSP00000551090.1
	AXIN2	ENST00000881032.1		c.*794C>T		3_prime_UTR	Exon 11 of 11	ENSP00000551091.1

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000488 AC: 4 AN: 81984 Hom.: 0 Cov.: 0 AF XY: 0.0000793 AC XY: 3 AN XY: 37850

African (AFR) AF: 0.000257 AC: 1 AN: 3896

American (AMR) AF: 0.00116 AC: 3 AN: 2582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5132

East Asian (EAS) AF: 0.00 AC: 0 AN: 11432

South Asian (SAS) AF: 0.00 AC: 0 AN: 734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 494

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 50774

Other (OTH) AF: 0.00 AC: 0 AN: 6790

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152108 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74294

African (AFR) AF: 0.000169 AC: 7 AN: 41426

American (AMR) AF: 0.000851 AC: 13 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5208

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 187

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.036
DANN	Benign	0.59
PhyloP100		-8.9
Mutation Taster		=100/0	polymorphism

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;