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NM_207122.2(EXT2):c.939+1G>T AND Exostoses, multiple, type 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 28, 2023
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:
RCV003499969.2

Allele description [Variation Report for NM_207122.2(EXT2):c.939+1G>T]

NM_207122.2(EXT2):c.939+1G>T

Gene:
EXT2:exostosin glycosyltransferase 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p11.2
Genomic location:
Preferred name:
NM_207122.2(EXT2):c.939+1G>T
HGVS:
  • NC_000011.10:g.44124985G>T
  • NG_007560.1:g.34437G>T
  • NM_000401.3:c.1038+1G>T
  • NM_001178083.3:c.939+1G>T
  • NM_001389628.1:c.939+1G>T
  • NM_001389630.1:c.939+1G>T
  • NM_207122.2:c.939+1G>TMANE SELECT
  • LRG_494t1:c.1038+1G>T
  • LRG_494:g.34437G>T
  • NC_000011.9:g.44146535G>T
Molecular consequence:
  • NM_000401.3:c.1038+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001178083.3:c.939+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001389628.1:c.939+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001389630.1:c.939+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_207122.2:c.939+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Exostoses, multiple, type 2 (EXT2)
Synonyms:
EXOSTOSES, MULTIPLE, TYPE II
Identifiers:
MONDO: MONDO:0007586; MedGen: C1851413; Orphanet: 321; OMIM: 133701

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004294767Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Sep 28, 2023) 		germlineclinical testing

PubMed (5)
[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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004294767.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change affects a donor splice site in intron 5 of the EXT2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in EXT2 are known to be pathogenic (PMID: 10679937, 19810120). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with multiple osteochondromas (PMID: 27748933). It has also been observed to segregate with disease in related individuals. Studies have shown that disruption of this splice site is associated with altered splicing resulting in multiple RNA products (PMID: 27748933). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024