rs7219582

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.1712+19G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,254 control chromosomes in the GnomAD database, including 11,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1939 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9750 hom. )

Consequence

AXIN2
NM_004655.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.07

Publications

9 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: 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

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=-0.93).

BP6

Variant 17-65537305-C-A is Benign according to our data. Variant chr17-65537305-C-A is described in ClinVar as Benign. ClinVar VariationId is 259512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN2	NM_004655.4 link	c.1712+19G>T		intron_variant	Intron 6 of 10	ENST00000307078.10	NP_004646.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
AXIN2	ENST00000307078.10 link	c.1712+19G>T	intron_variant	Intron 6 of 10	1	NM_004655.4	ENSP00000302625.5
AXIN2	ENST00000375702.5 link	c.1712+19G>T	intron_variant	Intron 5 of 8	1		ENSP00000364854.5
AXIN2	ENST00000618960.4 link	c.1712+19G>T	intron_variant	Intron 6 of 9	5		ENSP00000478916.1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22342

AN:

152002

Hom.:

1934

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.0574

Gnomad MID

AF:

0.245

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.168

GnomAD2 exomes

AF:

0.119

AC:

29684

AN:

249130

AF XY:

0.120

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.0796

Gnomad ASJ exome

AF:

0.140

Gnomad EAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.0662

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.110

AC:

160860

AN:

1461134

Hom.:

9750

Cov.:

AF XY:

0.112

AC XY:

81634

AN XY:

726898

show subpopulations

African (AFR)

AF:

0.253

AC:

8472

AN:

33460

American (AMR)

AF:

0.0845

AC:

3777

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

3665

AN:

26136

East Asian (EAS)

AF:

0.121

AC:

4814

AN:

39696

South Asian (SAS)

AF:

0.164

AC:

14126

AN:

86218

European-Finnish (FIN)

AF:

0.0647

AC:

3451

AN:

53364

Middle Eastern (MID)

AF:

0.206

AC:

1104

AN:

5362

European-Non Finnish (NFE)

AF:

0.102

AC:

113755

AN:

1111830

Other (OTH)

AF:

0.128

AC:

7696

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

8506

17012

25518

34024

42530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4206

8412

12618

16824

21030

<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:

0.147

AC:

22370

AN:

152120

Hom.:

1939

Cov.:

AF XY:

0.145

AC XY:

10747

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.246

AC:

10202

AN:

41486

American (AMR)

AF:

0.116

AC:

1776

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

459

AN:

3472

East Asian (EAS)

AF:

0.111

AC:

567

AN:

5120

South Asian (SAS)

AF:

0.169

AC:

818

AN:

4826

European-Finnish (FIN)

AF:

0.0574

AC:

608

AN:

10596

Middle Eastern (MID)

AF:

0.243

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.109

AC:

7443

AN:

68008

Other (OTH)

AF:

0.166

AC:

352

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

911

1822

2734

3645

4556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<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:

0.126

Hom.:

2141

Bravo

AF:

0.153

Asia WGS

AF:

0.133

AC:

463

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 27, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: The variant of interest is located at a non-conserved intronic position, not widely known to affect splicing, with 5/5 in silico programs via Alamut predicting no significant effect on splicing, although these predictions have yet to be functionally assessed. The variant of interest has been observed in the large, broad control population, ExAC, with an allele frequency of 14771/121216 (1/8 including 1069 homozygotes), which exceeds the predicted maximum expected allele frequency for a pathogenic AXIN2 variant of 1/7037. The variant of interest has been reported in affected individuals via publications with a classification of "polymorphism." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Benign. -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oligodontia-cancer predisposition syndrome

Benign:2

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.022

(source)

DANN

Benign

0.59

PhyloP100

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over