17-65549504-T-C

Variant names:

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.956+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0586 in 1,611,332 control chromosomes in the GnomAD database, including 4,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 847 hom., cov: 32)

Exomes 𝑓: 0.056 ( 3953 hom. )

Consequence

AXIN2
NM_004655.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.674

Publications

17 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:

ENSG00000266076 (HGNC:):

ENSG00000266076 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=-0.85).

BP6

Variant 17-65549504-T-C is Benign according to our data. Variant chr17-65549504-T-C is described in ClinVar as Benign. ClinVar VariationId is 259516.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN2	NM_004655.4 link	c.956+16A>G		intron_variant	Intron 3 of 10	ENST00000307078.10	NP_004646.3	Q9Y2T1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
AXIN2	ENST00000307078.10 link	c.956+16A>G	intron_variant	Intron 3 of 10	1	NM_004655.4	ENSP00000302625.5	Q9Y2T1
AXIN2	ENST00000375702.5 link	c.956+16A>G	intron_variant	Intron 2 of 8	1		ENSP00000364854.5	E7ES00
ENSG00000266076	ENST00000577662.1 link	n.*1132+16A>G	intron_variant	Intron 5 of 6	2		ENSP00000462418.1	J3KSC3
AXIN2	ENST00000618960.4 link	c.956+16A>G	intron_variant	Intron 3 of 9	5		ENSP00000478916.1	E7ES00

Frequencies

GnomAD3 genomes

AF:

0.0862

AC:

13104

AN:

151982

Hom.:

828

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.0644

Gnomad FIN

AF:

0.0735

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0427

Gnomad OTH

AF:

0.0738

GnomAD2 exomes

AF:

0.0833

AC:

20597

AN:

247344

AF XY:

0.0774

show subpopulations

Gnomad AFR exome

AF:

0.125

Gnomad AMR exome

AF:

0.155

Gnomad ASJ exome

AF:

0.0194

Gnomad EAS exome

AF:

0.274

Gnomad FIN exome

AF:

0.0709

Gnomad NFE exome

AF:

0.0395

Gnomad OTH exome

AF:

0.0689

GnomAD4 exome

AF:

0.0557

AC:

81226

AN:

1459232

Hom.:

3953

Cov.:

AF XY:

0.0550

AC XY:

39948

AN XY:

725728

show subpopulations

African (AFR)

AF:

0.131

AC:

4374

AN:

33412

American (AMR)

AF:

0.154

AC:

6842

AN:

44424

Ashkenazi Jewish (ASJ)

AF:

0.0189

AC:

494

AN:

26114

East Asian (EAS)

AF:

0.296

AC:

11714

AN:

39530

South Asian (SAS)

AF:

0.0581

AC:

4980

AN:

85718

European-Finnish (FIN)

AF:

0.0669

AC:

3564

AN:

53268

Middle Eastern (MID)

AF:

0.0558

AC:

302

AN:

5408

European-Non Finnish (NFE)

AF:

0.0409

AC:

45420

AN:

1111074

Other (OTH)

AF:

0.0587

AC:

3536

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

4216

8432

12648

16864

21080

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1988

3976

5964

7952

9940

<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:

0.0865

AC:

13156

AN:

152100

Hom.:

847

Cov.:

AF XY:

0.0916

AC XY:

6809

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.126

AC:

5231

AN:

41480

American (AMR)

AF:

0.147

AC:

2249

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

AN:

3468

East Asian (EAS)

AF:

0.272

AC:

1407

AN:

5174

South Asian (SAS)

AF:

0.0635

AC:

305

AN:

4806

European-Finnish (FIN)

AF:

0.0735

AC:

778

AN:

10580

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0427

AC:

2905

AN:

67998

Other (OTH)

AF:

0.0854

AC:

180

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

581

1163

1744

2326

2907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.0587

Hom.:

297

Bravo

AF:

0.0916

Asia WGS

AF:

0.189

AC:

657

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

not provided

Benign:3

Apr 28, 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 c.956+16A>G variant affects a non-conserved intronic nucleotide at an intronic position not widely known to affect splicing. MutationTaster predicts benign outcome for this variant. In addition, 5/5 splice-site tools in Alamut predict that this variant does not affect normal splicing. This variant is found in 9192/108058 control chromosomes from the large and broad populations of ExAC (including 609 homozygotes) at a frequency of 0.0850654, which is about 599 times greater than the maximal expected frequency of a pathogenic allele (0.0001421) in this gene, suggesting this variant is benign. Taken together, this variant has been classified as Benign. -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.85

CADD

Benign

0.051

(source)

DANN

Benign

0.24

PhyloP100

-0.67

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)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over