rs878854720

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.129C>T(p.Gly43Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,459,576 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 (★★). Synonymous variant affecting the same amino acid position (i.e. G43G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

AXIN2
NM_004655.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.866

Publications

0 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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 17-65558492-G-A is Benign according to our data. Variant chr17-65558492-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 239982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65558492-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 239982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65558492-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 239982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65558492-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 239982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65558492-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 239982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65558492-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 239982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65558492-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 239982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65558492-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 239982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65558492-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 239982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65558492-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 239982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65558492-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 239982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65558492-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 239982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65558492-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 239982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65558492-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 239982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65558492-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 239982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65558492-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 239982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.866 with no splicing effect.

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN2	NM_004655.4 link	c.129C>T	p.Gly43Gly	synonymous_variant	Exon 2 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.129C>T	p.Gly43Gly	synonymous_variant	Exon 2 of 11	1	NM_004655.4	ENSP00000302625.5	Q9Y2T1
ENSG00000266076	ENST00000577662.1 link	n.*305C>T		non_coding_transcript_exon_variant	Exon 4 of 7	2		ENSP00000462418.1	J3KSC3
ENSG00000266076	ENST00000577662.1 link	n.*305C>T		3_prime_UTR_variant	Exon 4 of 7	2		ENSP00000462418.1	J3KSC3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1459576

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725788

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33446

American (AMR)

AF:

0.00

AC:

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25940

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39638

South Asian (SAS)

AF:

0.00

AC:

AN:

86082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53292

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1110488

Other (OTH)

AF:

0.0000166

AC:

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.0000877

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Oligodontia-cancer predisposition syndrome

Benign:2

Jun 25, 2024

Myriad Genetics, Inc.

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -

Mar 11, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jun 27, 2016

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Hereditary cancer-predisposing syndrome

Benign:1

Apr 25, 2022

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

-0.59

CADD

Benign

9.9

(source)

DANN

Benign

0.92

PhyloP100

0.87

PromoterAI

-0.018

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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