17-65549504-T-C

Position:

chr17-65549504-T-C

Variant summary

Our verdict is Benign. Variant got -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:8

Conservation

PhyloP100: -0.674

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 259516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65549504-T-C is described in Lovd as [Benign].

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/exons	MANE	UniProt
AXIN2	NM_004655.4 linkuse as main transcript	c.956+16A>G		intron_variant		ENST00000307078.10

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
AXIN2	ENST00000307078.10 linkuse as main transcript	c.956+16A>G	intron_variant	1	NM_004655.4	P1
AXIN2	ENST00000375702.5 linkuse as main transcript	c.956+16A>G	intron_variant	1
AXIN2	ENST00000618960.4 linkuse as main transcript	c.956+16A>G	intron_variant	5

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

GnomAD3 exomes

AF:

0.0833

AC:

20597

AN:

247344

Hom.:

1423

AF XY:

0.0774

AC XY:

10354

AN XY:

133700

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 SAS exome

AF:

0.0604

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

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.154

Gnomad4 ASJ exome

AF:

0.0189

Gnomad4 EAS exome

AF:

0.296

Gnomad4 SAS exome

AF:

0.0581

Gnomad4 FIN exome

AF:

0.0669

Gnomad4 NFE exome

AF:

0.0409

Gnomad4 OTH exome

AF:

0.0587

GnomAD4 genome

AF:

0.0865

AC:

13156

AN:

152100

Hom.:

847

Cov.:

AF XY:

0.0916

AC XY:

6809

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.147

Gnomad4 ASJ

AF:

0.0225

Gnomad4 EAS

AF:

0.272

Gnomad4 SAS

AF:

0.0635

Gnomad4 FIN

AF:

0.0735

Gnomad4 NFE

AF:

0.0427

Gnomad4 OTH

AF:

0.0854

Alfa

AF:

0.0521

Hom.:

110

Bravo

AF:

0.0916

Asia WGS

AF:

0.189

AC:

657

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Oligodontia-cancer predisposition syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 28, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.051

DANN

Benign

0.24

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over