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NM_003482.4(KMT2D):c.5707C>T (p.Arg1903Ter) AND Kabuki syndrome 1

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Mar 31, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001249645.6

Allele description [Variation Report for NM_003482.4(KMT2D):c.5707C>T (p.Arg1903Ter)]

NM_003482.4(KMT2D):c.5707C>T (p.Arg1903Ter)

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.5707C>T (p.Arg1903Ter)
HGVS:
  • NC_000012.12:g.49042816G>A
  • NG_027827.1:g.17509C>T
  • NM_003482.4:c.5707C>TMANE SELECT
  • NP_003473.3:p.Arg1903Ter
  • NP_003473.3:p.Arg1903Ter
  • NC_000012.11:g.49436599G>A
  • NM_003482.3:c.5707C>T
Protein change:
R1903*
Links:
dbSNP: rs886041405
NCBI 1000 Genomes Browser:
rs886041405
Molecular consequence:
  • NM_003482.4:c.5707C>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001423661Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jul 13, 2017) 		germlineclinical testing

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

SCV004014745Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSLVariantClassificationCriteria RUGD 01 April 2020)		Pathogenic
(Mar 31, 2023) 		unknownclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical 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

MLL2 and KDM6A mutations in patients with Kabuki syndrome.

Miyake N, Koshimizu E, Okamoto N, Mizuno S, Ogata T, Nagai T, Kosho T, Ohashi H, Kato M, Sasaki G, Mabe H, Watanabe Y, Yoshino M, Matsuishi T, Takanashi J, Shotelersuk V, Tekin M, Ochi N, Kubota M, Ito N, Ihara K, Hara T, et al.

Am J Med Genet A. 2013 Sep;161A(9):2234-43. doi: 10.1002/ajmg.a.36072. Epub 2013 Aug 2.

PubMed [citation]
PMID:
23913813
See all PubMed Citations (7)

Details of each submission

From Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital, SCV001423661.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

[ACMG/AMP: PVS1, PM2, PM6, PP3, PP5] This alteration is a null variant in a gene where LOF is a known mechanism of disease [PVS1], is absent from or rarely observed in large-scale population databases [PM2], is de novo in origin as it was not detected in the submitted parental specimens (identity NOT confirmed) [PM6], is predicted to be damaging by multiple functional prediction tools [PP3], was reported as a pathogenic/likely pathogenic alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory) [PP5].

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Illumina Laboratory Services, Illumina, SCV004014745.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

The KMT2D c.5707C>T (p.Arg1903Ter) results in a premature termination of the protein at amino acid position 1903. Loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay is expected. This variant has been reported in a heterozygous state in six individuals with Kabuki syndrome, including in a confirmed de novo state in two individuals (PMID: 23913813; PMID: 25281733; PMID: 27302555; PMID: 30107592; PMID: 32371413; PMID: 30266093). This variant is not found in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. This variant was identified in a de novo state. Based on the available evidence, the c.5707C>T (p.Arg1903Ter) variant is classified as pathogenic for Kabuki syndrome.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024