chr17-65537650-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004655.4(AXIN2):c.1386C>T(p.Pro462Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,570,832 control chromosomes in the GnomAD database, including 317,138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.53 ( 23264 hom., cov: 32)

Exomes 𝑓: 0.64 ( 293874 hom. )

Consequence

AXIN2
NM_004655.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:20O:1

Conservation

PhyloP100: -0.688

Publications

42 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 17-65537650-G-A is Benign according to our data. Variant chr17-65537650-G-A is described in ClinVar as Benign. ClinVar VariationId is 259510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.688 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.647 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.1386C>T	p.Pro462Pro	synonymous	Exon 6 of 11	NP_004646.3	Q9Y2T1
	AXIN2	NM_001363813.1		c.1386C>T	p.Pro462Pro	synonymous	Exon 6 of 10	NP_001350742.1	E7ES00

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AXIN2	ENST00000307078.10	TSL:1 MANE Select	c.1386C>T	p.Pro462Pro	synonymous	Exon 6 of 11	ENSP00000302625.5	Q9Y2T1
AXIN2	ENST00000375702.5	TSL:1	c.1386C>T	p.Pro462Pro	synonymous	Exon 5 of 9	ENSP00000364854.5	E7ES00
AXIN2	ENST00000881031.1		c.1386C>T	p.Pro462Pro	synonymous	Exon 6 of 11	ENSP00000551090.1

Frequencies

GnomAD3 genomes

AF:

0.528

AC:

80129

AN:

151668

Hom.:

23271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.777

Gnomad AMR

AF:

0.562

Gnomad ASJ

AF:

0.720

Gnomad EAS

AF:

0.350

Gnomad SAS

AF:

0.606

Gnomad FIN

AF:

0.618

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.652

Gnomad OTH

AF:

0.547

GnomAD2 exomes

AF:

0.600

AC:

111518

AN:

185902

AF XY:

0.607

show subpopulations

Gnomad AFR exome

AF:

0.272

Gnomad AMR exome

AF:

0.605

Gnomad ASJ exome

AF:

0.720

Gnomad EAS exome

AF:

0.352

Gnomad FIN exome

AF:

0.623

Gnomad NFE exome

AF:

0.664

Gnomad OTH exome

AF:

0.617

GnomAD4 exome

AF:

0.637

AC:

904596

AN:

1419046

Hom.:

293874

Cov.:

AF XY:

0.637

AC XY:

447561

AN XY:

702442

show subpopulations

African (AFR)

AF:

0.272

AC:

8959

AN:

32954

American (AMR)

AF:

0.598

AC:

22319

AN:

37326

Ashkenazi Jewish (ASJ)

AF:

0.717

AC:

18290

AN:

25498

East Asian (EAS)

AF:

0.340

AC:

12963

AN:

38124

South Asian (SAS)

AF:

0.615

AC:

50996

AN:

82884

European-Finnish (FIN)

AF:

0.619

AC:

27841

AN:

44960

Middle Eastern (MID)

AF:

0.585

AC:

3288

AN:

5618

European-Non Finnish (NFE)

AF:

0.663

AC:

724107

AN:

1092622

Other (OTH)

AF:

0.607

AC:

35833

AN:

59060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

21117

42234

63350

84467

105584

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18846

37692

56538

75384

94230

<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:

0.528

AC:

80138

AN:

151786

Hom.:

23264

Cov.:

AF XY:

0.526

AC XY:

38972

AN XY:

74106

show subpopulations

African (AFR)

AF:

0.279

AC:

11576

AN:

41458

American (AMR)

AF:

0.561

AC:

8569

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.720

AC:

2500

AN:

3470

East Asian (EAS)

AF:

0.351

AC:

1762

AN:

5020

South Asian (SAS)

AF:

0.607

AC:

2917

AN:

4808

European-Finnish (FIN)

AF:

0.618

AC:

6512

AN:

10544

Middle Eastern (MID)

AF:

0.561

AC:

165

AN:

294

European-Non Finnish (NFE)

AF:

0.652

AC:

44291

AN:

67900

Other (OTH)

AF:

0.540

AC:

1139

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1740

3479

5219

6958

8698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<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:

0.600

Hom.:

5229

Bravo

AF:

0.515

Asia WGS

AF:

0.442

AC:

1539

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Oligodontia-cancer predisposition syndrome (5)

Hereditary cancer-predisposing syndrome (4)

not provided (5)

Carcinoma of colon;C1837750:Oligodontia-cancer predisposition syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

4.7

(source)

DANN

Benign

0.89

PhyloP100

-0.69

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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