17-65537827-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004655.4(AXIN2):c.1209G>A(p.Glu403Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000427 in 1,405,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

AXIN2
NM_004655.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.13

Publications

1 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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 17-65537827-C-T is Benign according to our data. Variant chr17-65537827-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2566129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.13 with no splicing effect.

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN2	NM_004655.4 link	c.1209G>A	p.Glu403Glu	synonymous_variant	Exon 6 of 11	ENST00000307078.10	NP_004646.3	Q9Y2T1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AXIN2	ENST00000307078.10 link	c.1209G>A	p.Glu403Glu	synonymous_variant	Exon 6 of 11	1	NM_004655.4	ENSP00000302625.5	Q9Y2T1
AXIN2	ENST00000375702.5 link	c.1209G>A	p.Glu403Glu	synonymous_variant	Exon 5 of 9	1		ENSP00000364854.5	E7ES00
AXIN2	ENST00000618960.4 link	c.1209G>A	p.Glu403Glu	synonymous_variant	Exon 6 of 10	5		ENSP00000478916.1	E7ES00

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000427

AC:

AN:

1405198

Hom.:

Cov.:

AF XY:

0.00000722

AC XY:

AN XY:

692752

show subpopulations

African (AFR)

AF:

0.0000314

AC:

AN:

31840

American (AMR)

AF:

0.00

AC:

AN:

36838

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23248

East Asian (EAS)

AF:

0.00

AC:

AN:

38458

South Asian (SAS)

AF:

0.00

AC:

AN:

77442

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50344

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5550

European-Non Finnish (NFE)

AF:

0.00000369

AC:

AN:

1083650

Other (OTH)

AF:

0.0000173

AC:

AN:

57828

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Oligodontia-cancer predisposition syndrome

Benign:1

Sep 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

May 15, 2023

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

3.9

(source)

DANN

Benign

0.62

PhyloP100

1.1

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

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17-65537827-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over