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NM_000127.3(EXT1):c.1057-2A>G AND Multiple congenital exostosis

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 21, 2019
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:
RCV000793605.10

Allele description [Variation Report for NM_000127.3(EXT1):c.1057-2A>G]

NM_000127.3(EXT1):c.1057-2A>G

Gene:
EXT1:exostosin glycosyltransferase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q24.11
Genomic location:
Preferred name:
NM_000127.3(EXT1):c.1057-2A>G
HGVS:
  • NC_000008.11:g.117835553T>C
  • NG_007455.2:g.281267A>G
  • NM_000127.3:c.1057-2A>GMANE SELECT
  • LRG_493t1:c.1057-2A>G
  • LRG_493:g.281267A>G
  • NC_000008.10:g.118847792T>C
  • NM_000127.2:c.1057-2A>G
Links:
dbSNP: rs1587003662
NCBI 1000 Genomes Browser:
rs1587003662
Molecular consequence:
  • NM_000127.3:c.1057-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Multiple congenital exostosis (EXT)
Synonyms:
MULTIPLE CARTILAGINOUS EXOSTOSES; Hereditary multiple osteochondromas; Multiple exostoses; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0005508; MedGen: C0015306; Orphanet: 321; OMIM: PS133700; Human Phenotype Ontology: HP:0002762

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000932967Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jul 21, 2019) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Molecular basis of multiple exostoses: mutations in the EXT1 and EXT2 genes.

Wuyts W, Van Hul W.

Hum Mutat. 2000;15(3):220-7. Review.

PubMed [citation]
PMID:
10679937
See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000932967.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in EXT1 are known to be pathogenic (PMID: 10679937, 11391482, 19810120). This variant has been observed in individuals affected with multiple osteochondromas (PMID: 9521425, 21499719). This variant is also known as IVS2-2A>G in the literature. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 2 of the EXT1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024