NM_207122.2(EXT2):c.473A>G (p.Asp158Gly) AND Exostoses, multiple, type 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 11, 2019
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:: RCV001225535.8

Allele description [Variation Report for NM_207122.2(EXT2):c.473A>G (p.Asp158Gly)]

NM_207122.2(EXT2):c.473A>G (p.Asp158Gly)

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.473A>G (p.Asp158Gly)

HGVS:

NC_000011.10:g.44108185A>G
NG_007560.1:g.17637A>G
NM_000401.3:c.572A>G
NM_001178083.3:c.473A>G
NM_001389628.1:c.473A>G
NM_001389630.1:c.473A>G
NM_207122.2:c.473A>GMANE SELECT
NP_000392.3:p.Asp191Gly
NP_001171554.1:p.Asp158Gly
NP_001376557.1:p.Asp158Gly
NP_001376559.1:p.Asp158Gly
NP_997005.1:p.Asp158Gly
LRG_494t1:c.572A>G
LRG_494t2:c.473A>G
LRG_494:g.17637A>G
LRG_494p1:p.Asp191Gly
NC_000011.9:g.44129735A>G
NM_207122.1:c.473A>G

Protein change:

D158G

Links:

dbSNP: rs1954089321

NCBI 1000 Genomes Browser:

rs1954089321

Molecular consequence:

NM_000401.3:c.572A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001178083.3:c.473A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001389628.1:c.473A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001389630.1:c.473A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_207122.2:c.473A>G - 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

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Profile neighbors for GEO Profiles (Select 61666650) (199)
GEO Profiles
Chromosome neighbors for GEO Profiles (Select 61711917) (20)
GEO Profiles
Homo sapiens inositol-tetrakisphosphate 1-kinase (ITPK1), RefSeqGene on chromoso...
Homo sapiens inositol-tetrakisphosphate 1-kinase (ITPK1), RefSeqGene on chromosome 14
gi|1042779829|ref|NG_051071.1|

Nucleotide
C10orf67 chromosome 10 open reading frame 67 [Homo sapiens]
C10orf67 chromosome 10 open reading frame 67 [Homo sapiens]
Gene ID:256815

Gene
Gene Links for GEO Profiles (Select 61666650) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001397818	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 11, 2019)	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

SCV001397818

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 11, 2019)

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, SCV001397818.5

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

Description

This sequence change replaces aspartic acid with glycine at codon 158 of the EXT2 protein (p.Asp158Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with EXT2-related conditions.

#	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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