NM_003482.4(KMT2D):c.8488C>T (p.Arg2830Ter) AND Kabuki syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 27, 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:: RCV001045940.7

Allele description [Variation Report for NM_003482.4(KMT2D):c.8488C>T (p.Arg2830Ter)]

NM_003482.4(KMT2D):c.8488C>T (p.Arg2830Ter)

Gene:

KMT2D:lysine methyltransferase 2D [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q13.12

Genomic location:

Preferred name:

NM_003482.4(KMT2D):c.8488C>T (p.Arg2830Ter)

HGVS:

NC_000012.12:g.49038868G>A
NG_027827.1:g.21457C>T
NM_003482.4:c.8488C>TMANE SELECT
NP_003473.3:p.Arg2830Ter
NP_003473.3:p.Arg2830Ter
NC_000012.11:g.49432651G>A
NM_003482.3:c.8488C>T
NP_003473.3:p.Arg2830*

Protein change:

R2830*

Links:

dbSNP: rs727503983

NCBI 1000 Genomes Browser:

rs727503983

Molecular consequence:

NM_003482.4:c.8488C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Kabuki syndrome
Synonyms:: Kabuki make-up syndrome; Niikawa-Kuroki syndrome
Identifiers:: MONDO: MONDO:0016512; MedGen: C0796004; OMIM: PS147920

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001209816	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 27, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22126750, 20711175, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001209816

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 27, 2019)

germline

clinical testing

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

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

Citations

PubMed

How genetically heterogeneous is Kabuki syndrome?: MLL2 testing in 116 patients, review and analyses of mutation and phenotypic spectrum.

Banka S, Veeramachaneni R, Reardon W, Howard E, Bunstone S, Ragge N, Parker MJ, Crow YJ, Kerr B, Kingston H, Metcalfe K, Chandler K, Magee A, Stewart F, McConnell VP, Donnelly DE, Berland S, Houge G, Morton JE, Oley C, Revencu N, Park SM, et al.

Eur J Hum Genet. 2012 Apr;20(4):381-8. doi: 10.1038/ejhg.2011.220. Epub 2011 Nov 30.

PubMed [citation]

PMID:: 22126750
PMCID:: PMC3306863

Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome.

Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, Beck AE, Tabor HK, Cooper GM, Mefford HC, Lee C, Turner EH, Smith JD, Rieder MJ, Yoshiura K, Matsumoto N, Ohta T, Niikawa N, Nickerson DA, Bamshad MJ, Shendure J.

Nat Genet. 2010 Sep;42(9):790-3. doi: 10.1038/ng.646. Epub 2010 Aug 15.

PubMed [citation]

PMID:: 20711175
PMCID:: PMC2930028

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001209816.5

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

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in KMT2D are known to be pathogenic (PMID: 22126750). This variant has been observed in individual(s) with Kabuki syndrome (PMID: 20711175). ClinVar contains an entry for this variant (Variation ID: 167222). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg2830*) in the KMT2D gene. It is expected to result in an absent or disrupted protein product.

#	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: Sep 29, 2024

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