NM_207122.2(EXT2):c.1019T>A (p.Val340Asp) AND Exostoses, multiple, type 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 13, 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:: RCV001104529.6

Allele description [Variation Report for NM_207122.2(EXT2):c.1019T>A (p.Val340Asp)]

NM_207122.2(EXT2):c.1019T>A (p.Val340Asp)

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.1019T>A (p.Val340Asp)

Other names:

EXT2, VAL373ASP (rs371996957)

HGVS:

NC_000011.10:g.44126895T>A
NG_007560.1:g.36347T>A
NM_000401.3:c.1118T>A
NM_001178083.3:c.1019T>A
NM_001389628.1:c.1019T>A
NM_001389630.1:c.1019T>A
NM_207122.2:c.1019T>AMANE SELECT
NP_000392.3:p.Val373Asp
NP_001171554.1:p.Val340Asp
NP_001376557.1:p.Val340Asp
NP_001376559.1:p.Val340Asp
NP_997005.1:p.Val340Asp
NP_997005.1:p.Val340Asp
LRG_494t1:c.1118T>A
LRG_494t2:c.1019T>A
LRG_494:g.36347T>A
LRG_494p1:p.Val373Asp
LRG_494p2:p.Val340Asp
NC_000011.9:g.44148445T>A
NM_207122.1:c.1019T>A

Protein change:

V340D; VAL373ASP

Links:

OMIM: 608210.0010; dbSNP: rs371996957

NCBI 1000 Genomes Browser:

rs371996957

Molecular consequence:

NM_000401.3:c.1118T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001178083.3:c.1019T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001389628.1:c.1019T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001389630.1:c.1019T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_207122.2:c.1019T>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

Clear Turn Off Turn On

LOC100221947 [Taeniopygia guttata]
LOC100221947 [Taeniopygia guttata]
Gene ID:100221947

Gene
PIGH [Taeniopygia guttata]
PIGH [Taeniopygia guttata]
Gene ID:100226775

Gene
LOC100227480 [Taeniopygia guttata]
LOC100227480 [Taeniopygia guttata]
Gene ID:100227480

Gene
LOC123234575 [Gracilinanus agilis]
LOC123234575 [Gracilinanus agilis]
Gene ID:123234575

Gene
NLRP10 NLR family pyrin domain containing 10 [Homo sapiens]
NLRP10 NLR family pyrin domain containing 10 [Homo sapiens]
Gene ID:338322

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001261402	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Jan 13, 2018)	germline	clinical testing	Citation Link,
SCV004300863	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 13, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30997052, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001261402

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Jan 13, 2018)

germline

clinical testing

Citation Link,

SCV004300863

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 13, 2023)

germline

clinical testing

PubMed (2)
[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

Developmental delay, coarse facial features, and epilepsy in a patient with EXT2 gene variants.

Gupta A, Ewing SA, Renaud DL, Hasadsri L, Raymond KM, Klee EW, Gavrilova RH.

Clin Case Rep. 2019 Apr;7(4):632-637. doi: 10.1002/ccr3.2010.

PubMed [citation]

PMID:: 30997052
PMCID:: PMC6452521

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 Illumina Laboratory Services, Illumina, SCV001261402.1

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004300863.1

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

Description

This variant is also known as c.1118T>A (p.Val373Asp). 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. 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 expected to disrupt EXT2 protein function. ClinVar contains an entry for this variant (Variation ID: 547989). This missense change has been observed in individual(s) with clinical features of autosomal recessive EXT2-related conditions (PMID: 30997052). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs371996957, gnomAD 0.003%). This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 340 of the EXT2 protein (p.Val340Asp).

#	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