NM_004655.4(AXIN2):c.1908-2A>G AND Oligodontia-cancer predisposition syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 21, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000640191.8

Allele description [Variation Report for NM_004655.4(AXIN2):c.1908-2A>G]

NM_004655.4(AXIN2):c.1908-2A>G

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.1908-2A>G

HGVS:

NC_000017.11:g.65536555T>C
NG_012142.1:g.30068A>G
NM_001363813.1:c.1713-2A>G
NM_004655.4:c.1908-2A>GMANE SELECT
LRG_296t1:c.1908-2A>G
LRG_296:g.30068A>G
NC_000017.10:g.63532673T>C
NM_004655.3:c.1908-2A>G

Links:

dbSNP: rs978837790

NCBI 1000 Genomes Browser:

rs978837790

Molecular consequence:

NM_001363813.1:c.1713-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_004655.4:c.1908-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000761780	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 21, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 30322717, 34196900, 15735151, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000761780

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 21, 2024)

germline

clinical testing

PubMed (4)
[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

Citations

PubMed

Germline pathogenic variants identified in women with ovarian tumors.

Carter NJ, Marshall ML, Susswein LR, Zorn KK, Hiraki S, Arvai KJ, Torene RI, McGill AK, Yackowski L, Murphy PD, Xu Z, Solomon BD, Klein RT, Hruska KS.

Gynecol Oncol. 2018 Dec;151(3):481-488. doi: 10.1016/j.ygyno.2018.09.030. Epub 2018 Oct 12.

PubMed [citation]

PMID:: 30322717

Germline variants in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer.

Ren M, Orozco A, Shao K, Albanez A, Ortiz J, Cao B, Wang L, Barreda L, Alvarez CS, Garland L, Wu D, Chung CC, Wang J, Frone M, Ralon S, Argueta V, Orozco R, Gharzouzi E, Dean M.

Breast Cancer Res Treat. 2021 Sep;189(2):533-539. doi: 10.1007/s10549-021-06305-5. Epub 2021 Jul 1. Erratum in: Breast Cancer Res Treat. 2022 Jan;191(1):227. doi: 10.1007/s10549-021-06373-7.

PubMed [citation]

PMID:: 34196900
PMCID:: PMC8357728

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000761780.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change affects an acceptor splice site in intron 7 of the AXIN2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (no rsID available, gnomAD 0.009%). Disruption of this splice site has been observed in individual(s) with breast or ovarian cancer (PMID: 30322717, 34196900). ClinVar contains an entry for this variant (Variation ID: 533167). Studies have shown that disruption of this splice site results in skipping of exon 7, but is expected to preserve the integrity of the reading-frame (Invitae). Tissue-specific alternative splicing of AXIN2 gene results in functional isoform lacking in-frame exon 7, also known as exon 6 (PMID: 15735151). For this reason the clinical significance of loss of exon 7 is currently uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Oct 26, 2024

ClinVar

Relating variation to medicine