NM_001278689.2(EOGT):c.1129C>T (p.Arg377Trp) AND Adams-Oliver syndrome 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 4, 2022
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:: RCV001889971.5

Allele description [Variation Report for NM_001278689.2(EOGT):c.1129C>T (p.Arg377Trp)]

NM_001278689.2(EOGT):c.1129C>T (p.Arg377Trp)

Gene:

EOGT:EGF domain specific O-linked N-acetylglucosamine transferase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p14.1

Genomic location:

Preferred name:

NM_001278689.2(EOGT):c.1129C>T (p.Arg377Trp)

HGVS:

NC_000003.12:g.68987468G>A
NG_042829.1:g.31427C>T
NM_001278689.2:c.1129C>TMANE SELECT
NM_173654.3:c.877C>T
NP_001265618.1:p.Arg377Trp
NP_775925.1:p.Arg293Trp
NC_000003.11:g.69036619G>A
NR_103826.2:n.1384C>T

Protein change:

R293W

Links:

dbSNP: rs377612780

NCBI 1000 Genomes Browser:

rs377612780

Molecular consequence:

NM_001278689.2:c.1129C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_173654.3:c.877C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_103826.2:n.1384C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Adams-Oliver syndrome 4 (AOS4)
Identifiers:: MONDO: MONDO:0014124; MedGen: C3809092; Orphanet: 974; OMIM: 615297

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002141617	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 4, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23522784, 25488668, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002141617

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 4, 2022)

germline

clinical testing

PubMed (3)
[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

Mutations in EOGT confirm the genetic heterogeneity of autosomal-recessive Adams-Oliver syndrome.

Shaheen R, Aglan M, Keppler-Noreuil K, Faqeih E, Ansari S, Horton K, Ashour A, Zaki MS, Al-Zahrani F, Cueto-González AM, Abdel-Salam G, Temtamy S, Alkuraya FS.

Am J Hum Genet. 2013 Apr 4;92(4):598-604. doi: 10.1016/j.ajhg.2013.02.012. Epub 2013 Mar 21.

PubMed [citation]

PMID:: 23522784
PMCID:: PMC3617382

Impaired O-linked N-acetylglucosaminylation in the endoplasmic reticulum by mutated epidermal growth factor (EGF) domain-specific O-linked N-acetylglucosamine transferase found in Adams-Oliver syndrome.

Ogawa M, Sawaguchi S, Kawai T, Nadano D, Matsuda T, Yagi H, Kato K, Furukawa K, Okajima T.

J Biol Chem. 2015 Jan 23;290(4):2137-49. doi: 10.1074/jbc.M114.598821. Epub 2014 Dec 8.

PubMed [citation]

PMID:: 25488668
PMCID:: PMC4303666

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002141617.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 293 of the EOGT protein (p.Arg293Trp). This variant is present in population databases (rs377612780, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with EOGT-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant disrupts the p.Arg293 amino acid residue in EOGT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23522784, 25488668). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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

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