NM_207122.2(EXT2):c.832G>A (p.Glu278Lys) AND Exostoses, multiple, type 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 8, 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:: RCV001049080.6

Allele description [Variation Report for NM_207122.2(EXT2):c.832G>A (p.Glu278Lys)]

NM_207122.2(EXT2):c.832G>A (p.Glu278Lys)

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.832G>A (p.Glu278Lys)

HGVS:

NC_000011.10:g.44124877G>A
NG_007560.1:g.34329G>A
NM_000401.3:c.931G>A
NM_001178083.3:c.832G>A
NM_001389628.1:c.832G>A
NM_001389630.1:c.832G>A
NM_207122.2:c.832G>AMANE SELECT
NP_000392.3:p.Glu311Lys
NP_001171554.1:p.Glu278Lys
NP_001376557.1:p.Glu278Lys
NP_001376559.1:p.Glu278Lys
NP_997005.1:p.Glu278Lys
LRG_494t1:c.931G>A
LRG_494t2:c.832G>A
LRG_494:g.34329G>A
LRG_494p1:p.Glu311Lys
NC_000011.9:g.44146427G>A
NM_207122.1:c.832G>A

Protein change:

E278K

Links:

dbSNP: rs117329700

NCBI 1000 Genomes Browser:

rs117329700

Molecular consequence:

NM_000401.3:c.931G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001178083.3:c.832G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001389628.1:c.832G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001389630.1:c.832G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_207122.2:c.832G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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glucan endo-1,3-beta-glucosidase 4 isoform X1 [Cucumis melo]
glucan endo-1,3-beta-glucosidase 4 isoform X1 [Cucumis melo]
gi|659097788|ref|XP_008449814.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001213114	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 8, 2023)	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

SCV001213114

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 8, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001213114.5

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

Description

Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt EXT2 protein function. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 278 of the EXT2 protein (p.Glu278Lys). This variant is present in population databases (rs117329700, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with EXT2-related conditions. This missense change has been observed to co-occur in individuals with a different variant in EXT2 that has been determined to be pathogenic (Invitae), but the significance of this finding is unclear. ClinVar contains an entry for this variant (Variation ID: 845913). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

ClinVar

Relating variation to medicine