Variant 17-65536247-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004655.4(AXIN2):c.2141+73G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 1,452,374 control chromosomes in the GnomAD database, including 3,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.054 ( 287 hom., cov: 33)

Exomes 𝑓: 0.063 ( 2900 hom. )

Consequence

AXIN2
NM_004655.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00700

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 17-65536247-C-T is Benign according to our data. Variant chr17-65536247-C-T is described in ClinVar as [Benign]. Clinvar id is 1247170.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.108 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.2141+73G>A		intron_variant		ENST00000307078.10

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
AXIN2	ENST00000307078.10 linkuse as main transcript	c.2141+73G>A	intron_variant	1	NM_004655.4	P1
AXIN2	ENST00000375702.5 linkuse as main transcript	c.1946+73G>A	intron_variant	1
AXIN2	ENST00000618960.4 linkuse as main transcript	c.1946+73G>A	intron_variant	5
AXIN2	ENST00000578251.1 linkuse as main transcript	n.363+73G>A	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0545

AC:

8287

AN:

152190

Hom.:

289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0255

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0396

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.0860

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0618

Gnomad OTH

AF:

0.0599

GnomAD4 exome

AF:

0.0635

AC:

82512

AN:

1300066

Hom.:

2900

AF XY:

0.0656

AC XY:

42360

AN XY:

646218

show subpopulations

Gnomad4 AFR exome

AF:

0.0222

Gnomad4 AMR exome

AF:

0.0303

Gnomad4 ASJ exome

AF:

0.0545

Gnomad4 EAS exome

AF:

0.0767

Gnomad4 SAS exome

AF:

0.120

Gnomad4 FIN exome

AF:

0.0971

Gnomad4 NFE exome

AF:

0.0592

Gnomad4 OTH exome

AF:

0.0684

GnomAD4 genome

AF:

0.0544

AC:

8282

AN:

152308

Hom.:

287

Cov.:

AF XY:

0.0574

AC XY:

4273

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0255

Gnomad4 AMR

AF:

0.0395

Gnomad4 ASJ

AF:

0.0493

Gnomad4 EAS

AF:

0.0854

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.102

Gnomad4 NFE

AF:

0.0617

Gnomad4 OTH

AF:

0.0588

Alfa

AF:

0.0567

Hom.:

Bravo

AF:

0.0479

Asia WGS

AF:

0.100

AC:

346

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.71

CADD

Benign

2.1

DANN

Benign

0.79

RBP_binding_hub_radar

0.77

RBP_regulation_power_radar

1.9

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