NM_207122.2(EXT2):c.1006C>T (p.Gln336Ter) AND Exostoses, multiple, type 2

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 27, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001204065.12

Allele description [Variation Report for NM_207122.2(EXT2):c.1006C>T (p.Gln336Ter)]

NM_207122.2(EXT2):c.1006C>T (p.Gln336Ter)

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.1006C>T (p.Gln336Ter)

HGVS:

NC_000011.10:g.44126882C>T
NG_007560.1:g.36334C>T
NM_000401.3:c.1105C>T
NM_001178083.3:c.1006C>T
NM_001389628.1:c.1006C>T
NM_001389630.1:c.1006C>T
NM_207122.2:c.1006C>TMANE SELECT
NP_000392.3:p.Gln369Ter
NP_001171554.1:p.Gln336Ter
NP_001376557.1:p.Gln336Ter
NP_001376559.1:p.Gln336Ter
NP_997005.1:p.Gln336Ter
LRG_494t1:c.1105C>T
LRG_494t2:c.1006C>T
LRG_494:g.36334C>T
LRG_494p1:p.Gln369Ter
NC_000011.9:g.44148432C>T
NM_207122.1:c.1006C>T

Protein change:

Q336*

Links:

dbSNP: rs1954414269

NCBI 1000 Genomes Browser:

rs1954414269

Molecular consequence:

NM_000401.3:c.1105C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001178083.3:c.1006C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001389628.1:c.1006C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001389630.1:c.1006C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_207122.2:c.1006C>T - 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
SCV001375253	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 27, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10679937, 19810120, 19504431, 28492532
SCV002061385	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 12, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001375253

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 27, 2023)

germline

clinical testing

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

SCV002061385

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 12, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001375253.5

#	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 creates a premature translational stop signal (p.Gln336*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hereditary multiple osteochondromatosis (PMID: 19504431). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 935468). For these reasons, this variant has been classified as Pathogenic.

#	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

From Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV002061385.2

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

Description

PVS1, PP1, PM2

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine