rs587778454

chr12-49050407-CC-AA

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2 BP6_Moderate

The NM_003482.4(KMT2D):c.3180_3181delinsTT(p.Lys1060_Val1061delinsAsnLeu) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KMT2D NM_003482.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 0.460

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 Likely_benign. Variant got -1 ACMG points.

• PP2: Missense variant where missense usually causes diseases, KMT2D
• BP6: Variant 12-49050407-CC-AA is Benign according to our data. Variant chr12-49050407-CC-AA is described in ClinVar as [Likely_benign]. Clinvar id is 134670.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMT2D	NM_003482.4	c.3180_3181delinsTT	p.Lys1060_Val1061delinsAsnLeu	missense_variant	12/55	ENST00000301067.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMT2D	ENST00000301067.12	c.3180_3181delinsTT	p.Lys1060_Val1061delinsAsnLeu	missense_variant	12/55	5	NM_003482.4	A2
KMT2D	ENST00000683543.2	c.3180_3181delinsTT	p.Lys1060_Val1061delinsAsnLeu	missense_variant	12/56			P4
KMT2D	ENST00000685166.1	c.3180_3181delinsTT	p.Lys1060_Val1061delinsAsnLeu	missense_variant	11/54			A2
KMT2D	ENST00000692637.1	c.3180_3181delinsTT	p.Lys1060_Val1061delinsAsnLeu	missense_variant	11/54			A2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Kabuki syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

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: rs587778454; hg19: chr12-49444190;