rs9906513

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004655.4(AXIN2):c.1907+39T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 1,611,606 control chromosomes in the GnomAD database, including 6,155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1442 hom., cov: 33)

Exomes 𝑓: 0.060 ( 4713 hom. )

Consequence

AXIN2
NM_004655.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.450

Publications

5 publications found

Variant links:

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

AXIN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 17-65536830-A-T is Benign according to our data. Variant chr17-65536830-A-T is described in ClinVar as Benign. ClinVar VariationId is 259513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 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.1907+39T>A		intron	N/A	NP_004646.3	Q9Y2T1
	AXIN2	NM_001363813.1		c.1713-277T>A		intron	N/A	NP_001350742.1	E7ES00

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AXIN2	ENST00000307078.10	TSL:1 MANE Select	c.1907+39T>A	intron	N/A	ENSP00000302625.5	Q9Y2T1
AXIN2	ENST00000375702.5	TSL:1	c.1713-277T>A	intron	N/A	ENSP00000364854.5	E7ES00
AXIN2	ENST00000881031.1		c.1907+39T>A	intron	N/A	ENSP00000551090.1

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16643

AN:

152106

Hom.:

1424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.0256

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.0602

Gnomad FIN

AF:

0.0726

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0445

Gnomad OTH

AF:

0.0946

GnomAD2 exomes

AF:

0.0908

AC:

22627

AN:

249180

AF XY:

0.0832

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.0217

Gnomad EAS exome

AF:

0.276

Gnomad FIN exome

AF:

0.0707

Gnomad NFE exome

AF:

0.0419

Gnomad OTH exome

AF:

0.0729

GnomAD4 exome

AF:

0.0596

AC:

87031

AN:

1459382

Hom.:

4713

Cov.:

AF XY:

0.0585

AC XY:

42508

AN XY:

726046

show subpopulations

African (AFR)

AF:

0.214

AC:

7158

AN:

33412

American (AMR)

AF:

0.157

AC:

7010

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0218

AC:

569

AN:

26132

East Asian (EAS)

AF:

0.303

AC:

12027

AN:

39698

South Asian (SAS)

AF:

0.0561

AC:

4836

AN:

86152

European-Finnish (FIN)

AF:

0.0659

AC:

3495

AN:

53052

Middle Eastern (MID)

AF:

0.0610

AC:

271

AN:

4446

European-Non Finnish (NFE)

AF:

0.0429

AC:

47719

AN:

1111552

Other (OTH)

AF:

0.0655

AC:

3946

AN:

60222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

4855

9710

14566

19421

24276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2124

4248

6372

8496

10620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.110

AC:

16705

AN:

152224

Hom.:

1442

Cov.:

AF XY:

0.113

AC XY:

8430

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.206

AC:

8571

AN:

41522

American (AMR)

AF:

0.151

AC:

2308

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0256

AC:

AN:

3472

East Asian (EAS)

AF:

0.272

AC:

1399

AN:

5146

South Asian (SAS)

AF:

0.0593

AC:

286

AN:

4826

European-Finnish (FIN)

AF:

0.0726

AC:

771

AN:

10618

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0446

AC:

3031

AN:

68016

Other (OTH)

AF:

0.106

AC:

224

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

713

1426

2139

2852

3565

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0368

Hom.:

Bravo

AF:

0.119

Asia WGS

AF:

0.197

AC:

686

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Oligodontia-cancer predisposition syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

3.2

(source)

DANN

Benign

0.84

PhyloP100

-0.45

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over