NM_004655.4(AXIN2):c.1994del (p.Gly665fs) AND Oligodontia-cancer predisposition syndrome

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

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 22, 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:: RCV000463233.9

Allele description

NM_004655.4(AXIN2):c.1994del (p.Gly665fs)

Gene:

AXIN2:axin 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17q24.1

Genomic location:

Preferred name:

NM_004655.4(AXIN2):c.1994del (p.Gly665fs)

Other names:

L688*

HGVS:

NC_000017.10:g.63532585del
NC_000017.11:g.65536473del
NG_012142.1:g.30156del
NM_001363813.1:c.1799del
NM_004655.4:c.1994delMANE SELECT
NP_001350742.1:p.Gly600fs
NP_004646.3:p.Gly665fs
LRG_296t1:c.1994del
LRG_296:g.30156del
LRG_296p1:p.Gly665Alafs
NC_000017.10:g.63532585del
NC_000017.10:g.63532585delC
NC_000017.10:g.63532591del
NM_004655.3:c.1994del
NM_004655.3:c.1994delG

Protein change:

G600fs; LEU688TER

Links:

OMIM: 604025.0002; dbSNP: rs267606674

NCBI 1000 Genomes Browser:

rs267606674

Molecular consequence:

NM_001363813.1:c.1799del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004655.4:c.1994del - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

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fp56e05.x3 zebrafish gridded kidney Danio rerio cDNA clone IMAGE:4760553 3', mRN...
fp56e05.x3 zebrafish gridded kidney Danio rerio cDNA clone IMAGE:4760553 3', mRNA sequence
gi|15303635|gnl|dbEST|9303907|gb|BI 0.1|

Nucleotide
protein sprouty homolog 1 [Mus musculus]
protein sprouty homolog 1 [Mus musculus]
gi|6755650|ref|NP_036026.1|

Protein
Mus musculus RIKEN cDNA 3110082I17 gene, mRNA (cDNA clone IMAGE:4017858), contai...
Mus musculus RIKEN cDNA 3110082I17 gene, mRNA (cDNA clone IMAGE:4017858), containing frame-shift errors
gi|28279979|gb|BC044867.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000548649	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 22, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15042511, 21416598, 28492532
SCV004045204	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

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000548649

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 22, 2023)

germline

clinical testing

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

SCV004045204

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

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 Invitae, SCV000548649.8

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

Description

This sequence change creates a premature translational stop signal (p.Gly665Alafs*24) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AXIN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 5880). For these reasons, this variant has been classified as Pathogenic.

#	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

From Myriad Genetics, Inc., SCV004045204.2

#	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 frameshift 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

Last Updated: May 1, 2024

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