17-65536399-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.2062C>T(p.Leu688Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0643 in 1,613,678 control chromosomes in the GnomAD database, including 6,154 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 (i.e. L688L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.11 ( 1473 hom., cov: 33)

Exomes 𝑓: 0.060 ( 4681 hom. )

Consequence

AXIN2
NM_004655.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 2.31

Publications

25 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=-0.55).

BP6

Variant 17-65536399-G-A is Benign according to our data. Variant chr17-65536399-G-A is described in ClinVar as Benign. ClinVar VariationId is 259514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 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.2062C>T	p.Leu688Leu	synonymous	Exon 8 of 11	NP_004646.3	Q9Y2T1
	AXIN2	NM_001363813.1		c.1867C>T	p.Leu623Leu	synonymous	Exon 7 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.2062C>T	p.Leu688Leu	synonymous	Exon 8 of 11	ENSP00000302625.5	Q9Y2T1
AXIN2	ENST00000375702.5	TSL:1	c.1867C>T	p.Leu623Leu	synonymous	Exon 6 of 9	ENSP00000364854.5	E7ES00
AXIN2	ENST00000881031.1		c.2062C>T	p.Leu688Leu	synonymous	Exon 8 of 11	ENSP00000551090.1

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16801

AN:

152144

Hom.:

1455

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.00769

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.0256

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.0595

Gnomad FIN

AF:

0.0724

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0444

Gnomad OTH

AF:

0.0927

GnomAD2 exomes

AF:

0.0911

AC:

22294

AN:

244814

AF XY:

0.0834

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.0216

Gnomad EAS exome

AF:

0.271

Gnomad FIN exome

AF:

0.0705

Gnomad NFE exome

AF:

0.0420

Gnomad OTH exome

AF:

0.0717

GnomAD4 exome

AF:

0.0595

AC:

86973

AN:

1461416

Hom.:

4681

Cov.:

AF XY:

0.0584

AC XY:

42421

AN XY:

727004

show subpopulations

African (AFR)

AF:

0.220

AC:

7373

AN:

33478

American (AMR)

AF:

0.157

AC:

7004

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.0217

AC:

567

AN:

26124

East Asian (EAS)

AF:

0.297

AC:

11793

AN:

39692

South Asian (SAS)

AF:

0.0550

AC:

4743

AN:

86234

European-Finnish (FIN)

AF:

0.0660

AC:

3503

AN:

53092

Middle Eastern (MID)

AF:

0.0653

AC:

376

AN:

5756

European-Non Finnish (NFE)

AF:

0.0429

AC:

47692

AN:

1111968

Other (OTH)

AF:

0.0649

AC:

3922

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

5267

10533

15800

21066

26333

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:

0.111

AC:

16862

AN:

152262

Hom.:

1473

Cov.:

AF XY:

0.114

AC XY:

8505

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.211

AC:

8771

AN:

41536

American (AMR)

AF:

0.150

AC:

2300

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0256

AC:

AN:

3470

East Asian (EAS)

AF:

0.268

AC:

1381

AN:

5162

South Asian (SAS)

AF:

0.0585

AC:

283

AN:

4834

European-Finnish (FIN)

AF:

0.0724

AC:

769

AN:

10618

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0444

AC:

3023

AN:

68022

Other (OTH)

AF:

0.104

AC:

220

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

731

1463

2194

2926

3657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

170

340

510

680

850

<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:

0.0667

Hom.:

268

Bravo

AF:

0.120

Asia WGS

AF:

0.193

AC:

670

AN:

3478

EpiCase

AF:

0.0402

EpiControl

AF:

0.0440

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Oligodontia-cancer predisposition syndrome (4)

Hereditary cancer-predisposing syndrome (3)

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

6.4

(source)

DANN

Benign

0.81

PhyloP100

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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

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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