NM_003482.4(KMT2D):c.15088C>T (p.Arg5030Cys) AND Kabuki syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 9, 2022
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:: RCV001857870.5

Allele description [Variation Report for NM_003482.4(KMT2D):c.15088C>T (p.Arg5030Cys)]

NM_003482.4(KMT2D):c.15088C>T (p.Arg5030Cys)

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.15088C>T (p.Arg5030Cys)

HGVS:

NC_000012.12:g.49026878G>A
NG_027827.1:g.33447C>T
NM_003482.4:c.15088C>TMANE SELECT
NP_003473.3:p.Arg5030Cys
NP_003473.3:p.Arg5030Cys
NC_000012.11:g.49420661G>A
NM_003482.3:c.15088C>T

Protein change:

R5030C

Links:

dbSNP: rs1555185875

NCBI 1000 Genomes Browser:

rs1555185875

Molecular consequence:

NM_003482.4:c.15088C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002118976	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 9, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23320472, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002118976

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 9, 2022)

germline

clinical testing

PubMed (2)
[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

MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype-phenotype study.

Makrythanasis P, van Bon BW, Steehouwer M, Rodríguez-Santiago B, Simpson M, Dias P, Anderlid BM, Arts P, Bhat M, Augello B, Biamino E, Bongers EM, Del Campo M, Cordeiro I, Cueto-González AM, Cuscó I, Deshpande C, Frysira E, Izatt L, Flores R, Galán E, Gener B, et al.

Clin Genet. 2013 Dec;84(6):539-45. doi: 10.1111/cge.12081. Epub 2013 Apr 26.

PubMed [citation]

PMID:: 23320472

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002118976.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KMT2D protein function. ClinVar contains an entry for this variant (Variation ID: 445885). This missense change has been observed in individual(s) with Kabuki syndrome (PMID: 23320472). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 5030 of the KMT2D protein (p.Arg5030Cys).

#	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: Feb 14, 2024

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