NM_207122.2(EXT2):c.1074G>A (p.Trp358Ter) AND Exostoses, multiple, type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 17, 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:: RCV000641565.5

Allele description [Variation Report for NM_207122.2(EXT2):c.1074G>A (p.Trp358Ter)]

NM_207122.2(EXT2):c.1074G>A (p.Trp358Ter)

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.1074G>A (p.Trp358Ter)

HGVS:

NC_000011.10:g.44126950G>A
NG_007560.1:g.36402G>A
NM_000401.3:c.1173G>A
NM_001178083.3:c.1074G>A
NM_001389628.1:c.1074G>A
NM_001389630.1:c.1074G>A
NM_207122.2:c.1074G>AMANE SELECT
NP_000392.3:p.Trp391Ter
NP_001171554.1:p.Trp358Ter
NP_001376557.1:p.Trp358Ter
NP_001376559.1:p.Trp358Ter
NP_997005.1:p.Trp358Ter
NP_997005.1:p.Trp358Ter
LRG_494t1:c.1173G>A
LRG_494t2:c.1074G>A
LRG_494:g.36402G>A
LRG_494p1:p.Trp391Ter
LRG_494p2:p.Trp358Ter
NC_000011.9:g.44148500G>A
NM_207122.1:c.1074G>A

Protein change:

W358*

Links:

dbSNP: rs1450980907

NCBI 1000 Genomes Browser:

rs1450980907

Molecular consequence:

NM_000401.3:c.1173G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001178083.3:c.1074G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001389628.1:c.1074G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001389630.1:c.1074G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_207122.2:c.1074G>A - nonsense - [Sequence Ontology: SO:0001587]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000763207	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 17, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23439489, 10679937, 19810120, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000763207

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 17, 2023)

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

Mutations in the EXT1 and EXT2 genes in Spanish patients with multiple osteochondromas.

Sarrión P, Sangorrin A, Urreizti R, Delgado A, Artuch R, Martorell L, Armstrong J, Anton J, Torner F, Vilaseca MA, Nevado J, Lapunzina P, Asteggiano CG, Balcells S, Grinberg D.

Sci Rep. 2013;3:1346. doi: 10.1038/srep01346.

PubMed [citation]

PMID:: 23439489
PMCID:: PMC3581825

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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000763207.4

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 534139). This premature translational stop signal has been observed in individual(s) with multiple osteochondromas (PMID: 19810120, 23439489). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp358*) in the EXT2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EXT2 are known to be pathogenic (PMID: 10679937, 19810120).

#	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: Sep 29, 2024

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