NM_003482.4(KMT2D):c.16501C>T (p.Arg5501Ter) AND Kabuki syndrome 1

Germline classification:: Pathogenic (3 submissions)
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:: RCV000578361.3

Allele description [Variation Report for NM_003482.4(KMT2D):c.16501C>T (p.Arg5501Ter)]

NM_003482.4(KMT2D):c.16501C>T (p.Arg5501Ter)

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.16501C>T (p.Arg5501Ter)

HGVS:

NC_000012.12:g.49022063G>A
NG_027827.1:g.38262C>T
NM_003482.4:c.16501C>TMANE SELECT
NP_003473.3:p.Arg5501Ter
NP_003473.3:p.Arg5501Ter
NC_000012.11:g.49415846G>A
NM_003482.3:c.16501C>T

Protein change:

R5501*

Links:

dbSNP: rs886041398

NCBI 1000 Genomes Browser:

rs886041398

Molecular consequence:

NM_003482.4:c.16501C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Kabuki syndrome 1 (KABUK1)
Identifiers:: MONDO: MONDO:0007843; MedGen: CN030661; Orphanet: 2322; OMIM: 147920

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000680121	Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	no assertion criteria provided (ACMG Guidelines, 2015)	Pathogenic (Jul 12, 2017)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001438163	Autoinflammatory diseases unit, CHU de Montpellier	no assertion criteria provided	Pathogenic (Apr 30, 2015)	unknown	clinical testing
SCV004013460	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 28884922, 20711175, 27302555, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000680121

Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals

no assertion criteria provided

(ACMG Guidelines, 2015)

Pathogenic
(Jul 12, 2017)

de novo

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001438163

Autoinflammatory diseases unit, CHU de Montpellier

no assertion criteria provided

Pathogenic
(Apr 30, 2015)

unknown

clinical testing

SCV004013460

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

unknown

clinical testing

PubMed (4)
[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	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Congenital heart defects in molecularly proven Kabuki syndrome patients.

Digilio MC, Gnazzo M, Lepri F, Dentici ML, Pisaneschi E, Baban A, Passarelli C, Capolino R, Angioni A, Novelli A, Marino B, Dallapiccola B.

Am J Med Genet A. 2017 Nov;173(11):2912-2922. doi: 10.1002/ajmg.a.38417. Epub 2017 Sep 8.

PubMed [citation]

PMID:: 28884922

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 (4)

Details of each submission

From Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals, SCV000680121.1

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

#	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

From Autoinflammatory diseases unit, CHU de Montpellier, SCV001438163.1

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

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

From 3billion, SCV004013460.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. This stop-gained (nonsense) variant is predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by less than 10%. The variant has been observed in at least two similarly affected unrelated individuals (PMID: 27302555). The variant has been previously reported as assumed (i.e. paternity and maternity not confirmed) de novo in at least two similarly affected unrelated individuals (PMID: 27302555, 28884922). The variant has been reported at least twice as pathogenic without evidence for the classification (ClinVar ID: VCV000280126/PMID: 20711175). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Mar 16, 2024

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