NM_207122.2(EXT2):c.514C>T (p.Gln172Ter) AND Exostoses, multiple, type 2

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 31, 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:: RCV000002576.11

Allele description [Variation Report for NM_207122.2(EXT2):c.514C>T (p.Gln172Ter)]

NM_207122.2(EXT2):c.514C>T (p.Gln172Ter)

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.514C>T (p.Gln172Ter)

HGVS:

NC_000011.10:g.44108226C>T
NG_007560.1:g.17678C>T
NM_000401.3:c.613C>T
NM_001178083.3:c.514C>T
NM_001389628.1:c.514C>T
NM_001389630.1:c.514C>T
NM_207122.2:c.514C>TMANE SELECT
NP_000392.3:p.Gln205Ter
NP_001171554.1:p.Gln172Ter
NP_001376557.1:p.Gln172Ter
NP_001376559.1:p.Gln172Ter
NP_997005.1:p.Gln172Ter
NP_997005.1:p.Gln172Ter
LRG_494t1:c.613C>T
LRG_494t2:c.514C>T
LRG_494:g.17678C>T
LRG_494p1:p.Gln205Ter
LRG_494p2:p.Gln172Ter
NC_000011.9:g.44129776C>T
NM_207122.1:c.514C>T

Protein change:

Q172*; GLN172TER

Links:

OMIM: 608210.0002; dbSNP: rs121918279

NCBI 1000 Genomes Browser:

rs121918279

Molecular consequence:

NM_000401.3:c.613C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001178083.3:c.514C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001389628.1:c.514C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001389630.1:c.514C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_207122.2:c.514C>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
SCV000022734	OMIM	no assertion criteria provided	Pathogenic (May 1, 2009)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 10679937, 19344451
SCV000815844	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 31, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 8894688, 9463333, 11432960, 17589361, 24496678, 10679937, 19810120, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000022734

OMIM

no assertion criteria provided

Pathogenic
(May 1, 2009)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000815844

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 31, 2023)

germline

clinical testing

PubMed (8)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

New mutations of EXT1 and EXT2 genes in German patients with Multiple Osteochondromas.

Heinritz W, Hüffmeier U, Strenge S, Miterski B, Zweier C, Leinung S, Bohring A, Mitulla B, Peters U, Froster UG.

Ann Hum Genet. 2009 May;73(Pt 3):283-91. doi: 10.1111/j.1469-1809.2009.00508.x. Epub 2009 Mar 25.

PubMed [citation]

PMID:: 19344451

Positional cloning of a gene involved in hereditary multiple exostoses.

Wuyts W, Van Hul W, Wauters J, Nemtsova M, Reyniers E, Van Hul EV, De Boulle K, de Vries BB, Hendrickx J, Herrygers I, Bossuyt P, Balemans W, Fransen E, Vits L, Coucke P, Nowak NJ, Shows TB, Mallet L, van den Ouweland AM, McGaughran J, Halley DJ, Willems PJ.

Hum Mol Genet. 1996 Oct;5(10):1547-57.

PubMed [citation]

PMID:: 8894688

See all PubMed Citations (9)

Details of each submission

From OMIM, SCV000022734.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In affected members of a large family with multiple exostoses II (EXT2; 133701) family, Wuyts et al. (1996) identified a 514C-T transition in the EXT2 gene, resulting in a gln172-to-ter (Q172X) substitution. The mutation was detected by SSCP analysis.

Heinritz et al. (2009) identified the Q172X mutation in a German patient with EXT2.

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000815844.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

ClinVar contains an entry for this variant (Variation ID: 2472). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individuals with hereditary multiple osteochondromatosis (PMID: 8894688, 9463333, 11432960, 17589361, 24496678). It has also been observed to segregate with disease in related individuals. This sequence change creates a premature translational stop signal (p.Gln172*) 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).

#	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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