NM_182931.3(KMT2E):c.2107G>T (p.Glu703Ter) AND Neurodevelopmental disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 30, 2019
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:: RCV001267669.1

Allele description [Variation Report for NM_182931.3(KMT2E):c.2107G>T (p.Glu703Ter)]

NM_182931.3(KMT2E):c.2107G>T (p.Glu703Ter)

Gene:

KMT2E:lysine methyltransferase 2E (inactive) [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q22.3

Genomic location:

Preferred name:

NM_182931.3(KMT2E):c.2107G>T (p.Glu703Ter)

HGVS:

NC_000007.14:g.105102105G>T
NG_033949.1:g.92916G>T
NM_018682.4:c.2107G>T
NM_182931.3:c.2107G>TMANE SELECT
NP_061152.3:p.Glu703Ter
NP_891847.1:p.Glu703Ter
LRG_1404t1:c.2107G>T
LRG_1404:g.92916G>T
LRG_1404p1:p.Glu703Ter
NC_000007.13:g.104742552G>T
NM_182931.2:c.2107G>T

Protein change:

E703*

Links:

dbSNP: rs1798679896

NCBI 1000 Genomes Browser:

rs1798679896

Molecular consequence:

NM_018682.4:c.2107G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_182931.3:c.2107G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Neurodevelopmental disorder
Identifiers:: MONDO: MONDO:0700092; MeSH: D065886; MedGen: C1535926

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001445897	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 30, 2019)	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

SCV001445897

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 30, 2019)

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	yes	not provided	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 Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV001445897.1

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

Description

This nonsense variant found in exon 17 of 27 is predicted to result in loss of normal protein function. This variant has not been previously reported or functionally characterized in the literature to our knowledge, though other loss of function variants have been described in affected individuals (PMID: 31079897). KMT2E is highly constrained and intolerant to loss of function variants (pLI score: 1.00). The variant is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.2107G>T (p.Glu703Ter) variant is classified as Pathogenic.

#	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

Last Updated: Apr 23, 2022

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