NM_207122.2(EXT2):c.1945C>T (p.Arg649Ter) AND Multiple exostoses type 2

Clinical significance:Conflicting interpretations of pathogenicity, Pathogenic(1);Uncertain significance(1) (Last evaluated: Mar 11, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV001039837.3

Allele description [Variation Report for NM_207122.2(EXT2):c.1945C>T (p.Arg649Ter)]

NM_207122.2(EXT2):c.1945C>T (p.Arg649Ter)

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.1945C>T (p.Arg649Ter)
HGVS:
  • NC_000011.10:g.44236302C>T
  • NG_007560.1:g.145754C>T
  • NM_000401.3:c.2044C>T
  • NM_001178083.2:c.1975C>T
  • NM_207122.2:c.1945C>TMANE SELECT
  • NP_000392.3:p.Arg682Ter
  • NP_001171554.1:p.Arg659Ter
  • NP_997005.1:p.Arg649Ter
  • LRG_494t1:c.2044C>T
  • LRG_494t2:c.1945C>T
  • LRG_494:g.145754C>T
  • LRG_494p1:p.Arg682Ter
  • NC_000011.9:g.44257852C>T
  • NM_207122.1:c.1945C>T
Protein change:
R649*
Links:
Molecular consequence:
  • NM_000401.3:c.2044C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001178083.2:c.1975C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_207122.2:c.1945C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Multiple exostoses 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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001203386Invitaecriteria provided, single submitter
Pathogenic
(Mar 11, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV001259402Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Jul 26, 2018)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Summary from all submissions

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

Citations

PubMed

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

Multiple osteochondromas: mutation update and description of the multiple osteochondromas mutation database (MOdb).

Jennes I, Pedrini E, Zuntini M, Mordenti M, Balkassmi S, Asteggiano CG, Casey B, Bakker B, Sangiorgi L, Wuyts W.

Hum Mutat. 2009 Dec;30(12):1620-7. doi: 10.1002/humu.21123. Review.

PubMed [citation]
PMID:
19810120
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001203386.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Arg649*) in the EXT2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs765648513, ExAC 0.008%). This variant has been observed in an individual affected with multiple osteochondromas (PMID: 19344451). Loss-of-function variants in EXT2 are known to be pathogenic (PMID: 10679937, 19810120). For these reasons, this variant has been classified as Pathogenic.

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

From Illumina Clinical Services Laboratory,Illumina, SCV001259402.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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

Last Updated: Aug 17, 2021

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