NM_024757.5(EHMT1):c.2725T>C (p.Cys909Arg) AND Kleefstra syndrome 1

Germline classification:: Pathogenic (1 submission)
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:: RCV004557281.2

Allele description [Variation Report for NM_024757.5(EHMT1):c.2725T>C (p.Cys909Arg)]

NM_024757.5(EHMT1):c.2725T>C (p.Cys909Arg)

Gene:

EHMT1:euchromatic histone lysine methyltransferase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.3

Genomic location:

Preferred name:

NM_024757.5(EHMT1):c.2725T>C (p.Cys909Arg)

HGVS:

NC_000009.12:g.137811473T>C
NG_011776.1:g.197482T>C
NM_001354263.2:c.2704T>C
NM_024757.5:c.2725T>CMANE SELECT
NP_001341192.1:p.Cys902Arg
NP_079033.4:p.Cys909Arg
NC_000009.11:g.140705925T>C

Protein change:

C902R

Links:

dbSNP: rs2538620071

NCBI 1000 Genomes Browser:

rs2538620071

Molecular consequence:

NM_001354263.2:c.2704T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_024757.5:c.2725T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Kleefstra syndrome 1
Identifiers:: MONDO: MONDO:0027407; MedGen: C0795833; Orphanet: 261494; OMIM: 610253

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005046462	HUSP Clinical Genetics Laboratory, Hospital Universitario San Pedro De Logroño (HUSP)	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	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

SCV005046462

HUSP Clinical Genetics Laboratory, Hospital Universitario San Pedro De Logroño (HUSP)

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

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	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 HUSP Clinical Genetics Laboratory, Hospital Universitario San Pedro De Logroño (HUSP), SCV005046462.1

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

Description

The variant was detected in a 21-years-old man with seizures and cognitive impairment. He presented the variant c.2725T>C in exon 19 of EHMT1 (NM_024757.5). It results in a substitution of amino acid (p.Cys909Arg). This variant is not detected in general population and has not been reported in pathogenic data bases.In silico tools predict that this variant affects the function of the protein and label it as pathogenic. The variant is detected in heterozygosis and is a “de novo” variant since it is not detected in the patient’s parents. Pathogenic variants in gen EHMT1 have been associated with Kleefstra Syndrome (OMIM: 610253), compatible with our patient’s phenotype; which includes neurodevelopment delay, and cognitive impairment. The classic form is associated with subtelomeric deletions but 25% of the cases are single nucleotide variants. Cognitive impairment is severe in the classic form, but mild to moderate cases have been reported. Other clinical features are diverse, including seizure, hypotonia and characteristic facies.

#	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		1	not provided	not provided	not provided

Last Updated: May 16, 2025

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