Variant 17-65536830-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004655.4(AXIN2):c.1907+39T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 1,611,606 control chromosomes in the GnomAD database, including 6,155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1442 hom., cov: 33)

Exomes 𝑓: 0.060 ( 4713 hom. )

Consequence

AXIN2
NM_004655.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.450

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 17-65536830-A-T is Benign according to our data. Variant chr17-65536830-A-T is described in ClinVar as [Benign]. Clinvar id is 259513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65536830-A-T 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	Protein	UniProt
AXIN2	NM_004655.4 linkuse as main transcript	c.1907+39T>A		intron_variant		ENST00000307078.10	NP_004646.3	Q9Y2T1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
AXIN2	ENST00000307078.10 linkuse as main transcript	c.1907+39T>A	intron_variant	1	NM_004655.4	ENSP00000302625.5	Q9Y2T1
AXIN2	ENST00000375702.5 linkuse as main transcript	c.1713-277T>A	intron_variant	1		ENSP00000364854.5	E7ES00
AXIN2	ENST00000618960.4 linkuse as main transcript	c.1713-277T>A	intron_variant	5		ENSP00000478916.1	E7ES00

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16643

AN:

152106

Hom.:

1424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.0256

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.0602

Gnomad FIN

AF:

0.0726

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0445

Gnomad OTH

AF:

0.0946

GnomAD3 exomes

AF:

0.0908

AC:

22627

AN:

249180

Hom.:

1759

AF XY:

0.0832

AC XY:

11233

AN XY:

134974

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.0217

Gnomad EAS exome

AF:

0.276

Gnomad SAS exome

AF:

0.0594

Gnomad FIN exome

AF:

0.0707

Gnomad NFE exome

AF:

0.0419

Gnomad OTH exome

AF:

0.0729

GnomAD4 exome

AF:

0.0596

AC:

87031

AN:

1459382

Hom.:

4713

Cov.:

AF XY:

0.0585

AC XY:

42508

AN XY:

726046

show subpopulations

Gnomad4 AFR exome

AF:

0.214

Gnomad4 AMR exome

AF:

0.157

Gnomad4 ASJ exome

AF:

0.0218

Gnomad4 EAS exome

AF:

0.303

Gnomad4 SAS exome

AF:

0.0561

Gnomad4 FIN exome

AF:

0.0659

Gnomad4 NFE exome

AF:

0.0429

Gnomad4 OTH exome

AF:

0.0655

GnomAD4 genome

AF:

0.110

AC:

16705

AN:

152224

Hom.:

1442

Cov.:

AF XY:

0.113

AC XY:

8430

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.206

Gnomad4 AMR

AF:

0.151

Gnomad4 ASJ

AF:

0.0256

Gnomad4 EAS

AF:

0.272

Gnomad4 SAS

AF:

0.0593

Gnomad4 FIN

AF:

0.0726

Gnomad4 NFE

AF:

0.0446

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.0368

Hom.:

Bravo

AF:

0.119

Asia WGS

AF:

0.197

AC:

686

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Oligodontia-cancer predisposition syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

3.2

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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