NM_003482.4(KMT2D):c.7998C>A (p.Asp2666Glu) AND Kabuki syndrome 1

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jun 11, 2020
Review status:: criteria provided, conflicting classifications

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:: RCV000659759.11

Allele description [Variation Report for NM_003482.4(KMT2D):c.7998C>A (p.Asp2666Glu)]

NM_003482.4(KMT2D):c.7998C>A (p.Asp2666Glu)

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.7998C>A (p.Asp2666Glu)

HGVS:

NC_000012.12:g.49039772G>T
NG_027827.1:g.20553C>A
NM_003482.4:c.7998C>AMANE SELECT
NP_003473.3:p.Asp2666Glu
NP_003473.3:p.Asp2666Glu
NC_000012.11:g.49433555G>T
NM_003482.3:c.7998C>A

Protein change:

D2666E

Links:

dbSNP: rs1258008817

NCBI 1000 Genomes Browser:

rs1258008817

Molecular consequence:

NM_003482.4:c.7998C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Mus musculus multiple coagulation factor deficiency 2 (Mcfd2), transcript varian...
Mus musculus multiple coagulation factor deficiency 2 (Mcfd2), transcript variant 1, mRNA
gi|284795212|ref|NM_176808.5|

Nucleotide
DNA methylase [Mycobacterium phage Ukulele]
DNA methylase [Mycobacterium phage Ukulele]
gi|918360333|gb|ALA06326.1|

Protein
lysin B [Mycobacterium phage TipsytheTRex]
lysin B [Mycobacterium phage TipsytheTRex]
gi|1269174130|gb|ATN92140.1|

Protein
yx25b04.r1 Soares melanocyte 2NbHM Homo sapiens cDNA clone IMAGE:262735 5' simil...
yx25b04.r1 Soares melanocyte 2NbHM Homo sapiens cDNA clone IMAGE:262735 5' similar to gb:M14338 VITAMIN K-DEPENDENT PROTEIN S PRECURSOR (HUMAN), mRNA sequence
gi|1146526|gnl|dbEST|429665|gb|N282

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000781608	Center for Human Genetics, Inc, Center for Human Genetics, Inc	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Nov 1, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001477913	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Uncertain significance (Jun 11, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000781608

Center for Human Genetics, Inc, Center for Human Genetics, Inc

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Nov 1, 2016)

germline

clinical testing

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

SCV001477913

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Uncertain significance
(Jun 11, 2020)

germline

clinical testing

Citation Link

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
not provided	germline	unknown	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 Center for Human Genetics, Inc, Center for Human Genetics, Inc, SCV000781608.1

#	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001477913.1

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

Description

The KMT2D c.7998C>A; p.Asp2666Glu variant (rs1258008817), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 447672). This variant is found in the general population with an overall allele frequency of 0.0029% (8/280302 alleles) in the Genome Aggregation Database. The aspartic acid at codon 2666 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of the p.Asp2666Glu variant is uncertain at this time.

#	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 16, 2024

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Relating variation to medicine