NM_024757.5(EHMT1):c.824-2del AND Kleefstra syndrome 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 3, 2020
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:: RCV001280600.1

Allele description [Variation Report for NM_024757.5(EHMT1):c.824-2del]

NM_024757.5(EHMT1):c.824-2del

Gene:

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

Variant type:

Deletion

Cytogenetic location:

9q34.3

Genomic location:

Preferred name:

NM_024757.5(EHMT1):c.824-2del

HGVS:

NC_000009.12:g.137743369del
NG_011776.1:g.129378del
NM_001145527.2:c.824-2del
NM_001354259.2:c.731-2del
NM_001354263.2:c.824-23del
NM_001354611.2:c.824-2del
NM_001354612.2:c.731-2del
NM_024757.5:c.824-2delMANE SELECT
NC_000009.11:g.140637821del
NC_000009.12:g.137743369_137743369delA
NM_024757.4:c.824-2delA

Links:

dbSNP: rs1234654104

NCBI 1000 Genomes Browser:

rs1234654104

Molecular consequence:

NM_001354263.2:c.824-23del - intron variant - [Sequence Ontology: SO:0001627]
NM_001145527.2:c.824-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354259.2:c.731-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354611.2:c.824-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354612.2:c.731-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_024757.5:c.824-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV001467812	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Dec 3, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001467812

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Dec 3, 2020)

germline

clinical testing

Citation Link

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001467812.1

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

Description

Variant summary: EHMT1 c.824-2delA is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict that the variant abolishes a 3-prime acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00011 in 210198 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.824-2delA in individuals affected with Kleefstra Syndrome 1 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	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: Jul 29, 2023

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