rs587778448

chr12-49051979-TTCAGGTGGCGGGGAAGTGGGCAATTCC-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_003482.4(KMT2D):c.1677_1703del(p.Glu560_Glu568del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KMT2D NM_003482.4 inframe_deletion
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 3.33

Genes affected

KMT2D (HGNC:7133): (lysine methyltransferase 2D) The protein encoded by this gene is a histone methyltransferase that methylates the Lys-4 position of histone H3. The encoded protein is part of a large protein complex called ASCOM, which has been shown to be a transcriptional regulator of the beta-globin and estrogen receptor genes. Mutations in this gene have been shown to be a cause of Kabuki syndrome. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_003482.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMT2D	NM_003482.4	c.1677_1703del	p.Glu560_Glu568del	inframe_deletion	11/55	ENST00000301067.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMT2D	ENST00000301067.12	c.1677_1703del	p.Glu560_Glu568del	inframe_deletion	11/55	5	NM_003482.4	A2
KMT2D	ENST00000683543.2	c.1677_1703del	p.Glu560_Glu568del	inframe_deletion	11/56			P4
KMT2D	ENST00000685166.1	c.1677_1703del	p.Glu560_Glu568del	inframe_deletion	10/54			A2
KMT2D	ENST00000692637.1	c.1677_1703del	p.Glu560_Glu568del	inframe_deletion	10/54			A2

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs587778448; hg19: chr12-49445762;