NM_003797.5(EED):c.581A>G (p.Asn194Ser) AND Cohen-Gibson syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Apr 25, 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:: RCV002273048.4

Allele description [Variation Report for NM_003797.5(EED):c.581A>G (p.Asn194Ser)]

NM_003797.5(EED):c.581A>G (p.Asn194Ser)

Gene:

EED:embryonic ectoderm development [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q14.2

Genomic location:

Preferred name:

NM_003797.5(EED):c.581A>G (p.Asn194Ser)

HGVS:

NC_000011.10:g.86257543A>G
NG_029595.1:g.17780A>G
NM_001308007.2:c.581A>G
NM_001330334.2:c.581A>G
NM_003797.5:c.581A>GMANE SELECT
NP_001294936.1:p.Asn194Ser
NP_001317263.1:p.Asn194Ser
NP_003788.2:p.Asn194Ser
NC_000011.9:g.85968585A>G
NM_003797.4:c.581A>G

Protein change:

N194S

Links:

dbSNP: rs1945710855

NCBI 1000 Genomes Browser:

rs1945710855

Molecular consequence:

NM_001308007.2:c.581A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330334.2:c.581A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003797.5:c.581A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cohen-Gibson syndrome (COGIS)
Identifiers:: MONDO: MONDO:0060510; MedGen: C4479654; OMIM: 617561

Recent activity

Clear Turn Off Turn On

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
SCV002557611	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 2, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28475857, 30858506, 25741868
SCV005043012	Institute of Immunology and Genetics Kaiserslautern	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 25, 2024)	de novo	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

SCV002557611

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 2, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV005043012

Institute of Immunology and Genetics Kaiserslautern

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 25, 2024)

de novo

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	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in Epigenetic Regulation Genes Are a Major Cause of Overgrowth with Intellectual Disability.

Tatton-Brown K, Loveday C, Yost S, Clarke M, Ramsay E, Zachariou A, Elliott A, Wylie H, Ardissone A, Rittinger O, Stewart F, Temple IK, Cole T; Childhood Overgrowth Collaboration, Mahamdallie S, Seal S, Ruark E, Rahman N.

Am J Hum Genet. 2017 May 4;100(5):725-736. doi: 10.1016/j.ajhg.2017.03.010.

PubMed [citation]

PMID:: 28475857
PMCID:: PMC5420355

Three additional patients with EED-associated overgrowth: potential mutation hotspots identified?

Spellicy CJ, Peng Y, Olewiler L, Cathey SS, Rogers RC, Bartholomew D, Johnson J, Alexov E, Lee JA, Friez MJ, Jones JR.

J Hum Genet. 2019 Jun;64(6):561-572. doi: 10.1038/s10038-019-0585-5. Epub 2019 Mar 11.

PubMed [citation]

PMID:: 30858506

See all PubMed Citations (3)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002557611.2

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

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0105 - The mechanism of disease for this gene is not clearly established. (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from asparagine to serine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported de novo in two unrelated individuals and in an unrelated family with Cohen-Gibson syndrome (PMID: 28475857, 30858506, Kang and Kim 2021). (SP) 0903 - This variant has limited evidence for segregation with disease. This variant segregated with disease in 4 members of the same family (Kang and Kim 2021). (SP) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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

From Institute of Immunology and Genetics Kaiserslautern, SCV005043012.1

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

Description

ACMG Criteria: PM2, PP5, PS2; Variant was found in heterozygous state

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

Last Updated: Aug 18, 2024

ClinVar

Relating variation to medicine