NM_004655.4(AXIN2):c.1988G>A (p.Trp663Ter) AND Oligodontia-cancer predisposition syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 17, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003337106.3

Allele description

NM_004655.4(AXIN2):c.1988G>A (p.Trp663Ter)

Gene:

AXIN2:axin 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q24.1

Genomic location:

Preferred name:

NM_004655.4(AXIN2):c.1988G>A (p.Trp663Ter)

HGVS:

NC_000017.11:g.65536473C>T
NG_012142.1:g.30150G>A
NM_001363813.1:c.1793G>A
NM_004655.4:c.1988G>AMANE SELECT
NP_001350742.1:p.Trp598Ter
NP_004646.3:p.Trp663Ter
NP_004646.3:p.Trp663Ter
LRG_296t1:c.1988G>A
LRG_296:g.30150G>A
LRG_296p1:p.Trp663Ter
NC_000017.10:g.63532591C>T
NM_004655.3:c.1988G>A

Protein change:

W598*

Molecular consequence:

NM_001363813.1:c.1793G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_004655.4:c.1988G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Oligodontia-cancer predisposition syndrome
Synonyms:: TOOTH AGENESIS-COLORECTAL CANCER SYNDROME; Oligodontia-colorectal cancer syndrome
Identifiers:: MONDO: MONDO:0012075; MedGen: C1837750; Orphanet: 300576; OMIM: 608615

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004045224	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (May 17, 2023)	unknown	clinical testing	Citation Link,
SCV004462538	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 8, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15042511, 21416598, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004045224

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Pathogenic
(May 17, 2023)

unknown

clinical testing

Citation Link,

SCV004462538

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 8, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer.

Lammi L, Arte S, Somer M, Jarvinen H, Lahermo P, Thesleff I, Pirinen S, Nieminen P.

Am J Hum Genet. 2004 May;74(5):1043-50. Epub 2004 Mar 23.

PubMed [citation]

PMID:: 15042511
PMCID:: PMC1181967

AXIN2-associated autosomal dominant ectodermal dysplasia and neoplastic syndrome.

Marvin ML, Mazzoni SM, Herron CM, Edwards S, Gruber SB, Petty EM.

Am J Med Genet A. 2011 Apr;155A(4):898-902. doi: 10.1002/ajmg.a.33927. Epub 2011 Mar 17.

PubMed [citation]

PMID:: 21416598
PMCID:: PMC3094478

See all PubMed Citations (3)

Details of each submission

From Myriad Genetics, Inc., SCV004045224.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV004462538.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with clinical features of AXIN2-related conditions (PMID: 21416598). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp663*) in the AXIN2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AXIN2 are known to be pathogenic (PMID: 15042511, 21416598).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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