NM_001278689.2(EOGT):c.1074del (p.Gly359fs) AND Adams-Oliver syndrome 4

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Apr 4, 2024
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:: RCV000049242.9

Allele description [Variation Report for NM_001278689.2(EOGT):c.1074del (p.Gly359fs)]

NM_001278689.2(EOGT):c.1074del (p.Gly359fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

3p14.1

Genomic location:

Preferred name:

NM_001278689.2(EOGT):c.1074del (p.Gly359fs)

HGVS:

NC_000003.12:g.68988305del
NG_042829.1:g.30591del
NM_001278689.2:c.1074delMANE SELECT
NM_173654.3:c.832-791del
NP_001265618.1:p.Gly359fs
NC_000003.11:g.69037456del
NM_001278689.1:c.1074del
NM_001278689.1:c.1074delA
NM_173654.1:c.832-791del
NM_173654.3:c.832-791del
NR_103826.2:n.1329del

Protein change:

G359fs

Links:

OMIM: 614789.0002; dbSNP: rs587776994

NCBI 1000 Genomes Browser:

rs587776994

Molecular consequence:

NM_001278689.2:c.1074del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_173654.3:c.832-791del - intron variant - [Sequence Ontology: SO:0001627]
NR_103826.2:n.1329del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

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
SCV000077495	OMIM	no assertion criteria provided	Pathogenic (Apr 4, 2013)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002012322	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 2, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004809444	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 4, 2024)	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

SCV000077495

OMIM

no assertion criteria provided

Pathogenic
(Apr 4, 2013)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV002012322

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 2, 2021)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004809444

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 4, 2024)

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	yes	1	not provided	not provided	1	not provided	clinical testing
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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000077495.3

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

Description

In a 2.67-year-old Arab boy with Adams-Oliver syndrome (AOS4; 615297), who was born of consanguineous parents, Shaheen et al. (2013) identified homozygosity for a 1-bp deletion (c.1074delA) in the EOGT gene, causing a frameshift that resulted in a premature stop codon (Gly359AspfsTer28). The mutation was not found in 230 Saudi exomes, the 1000 Genomes Project, or the NHLBI Exome Variant Server. In addition to cutis aplasia of the scalp and terminal transverse defects of the toes that were more pronounced on the right, he had a muscular ventricular septal defect and patent ductus arteriosus, which had resolved. Additional features included left temporal and occipital lobe infarcts of presumed prenatal origin, speech and fine motor delays, and umbilical hernia. Shaheen et al. (2013) stated that using the alternatively spliced NCBI version of EOGT (GenBank NM_173654.1), the mutation would be designated 832-791delA.

#	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 3billion, SCV002012322.1

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

Description

Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant has been reported as pathogenic/likely pathogenic without evidence for the classification (ClinVar ID: VCV000523612.1). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

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

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004809444.1

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

#	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: Apr 15, 2024

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