Variant rs34546217 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_003482.4(KMT2D):c.16412+16del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,602,132 control chromosomes in the GnomAD database, including 96,375 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6630 hom., cov: 23)

Exomes 𝑓: 0.35 ( 89745 hom. )

Consequence

KMT2D
NM_003482.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.832

Variant links:

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]

KMT2D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 12-49022263-TC-T is Benign according to our data. Variant chr12-49022263-TC-T is described in ClinVar as [Benign]. Clinvar id is 94193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49022263-TC-T is described in Lovd as [Likely_benign]. Variant chr12-49022263-TC-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KMT2D	NM_003482.4 linkuse as main transcript	c.16412+16del		intron_variant		ENST00000301067.12	NP_003473.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KMT2D	ENST00000301067.12 linkuse as main transcript	c.16412+16del		intron_variant		5	NM_003482.4	ENSP00000301067	A2	O14686-1

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40444

AN:

151964

Hom.:

6631

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0757

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.424

Gnomad SAS

AF:

0.423

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.349

Gnomad OTH

AF:

0.261

GnomAD3 exomes

AF:

0.320

AC:

79303

AN:

247488

Hom.:

13735

AF XY:

0.331

AC XY:

44441

AN XY:

134242

show subpopulations

Gnomad AFR exome

AF:

0.0639

Gnomad AMR exome

AF:

0.230

Gnomad ASJ exome

AF:

0.228

Gnomad EAS exome

AF:

0.435

Gnomad SAS exome

AF:

0.400

Gnomad FIN exome

AF:

0.364

Gnomad NFE exome

AF:

0.343

Gnomad OTH exome

AF:

0.322

GnomAD4 exome

AF:

0.346

AC:

501016

AN:

1450050

Hom.:

89745

Cov.:

AF XY:

0.347

AC XY:

249913

AN XY:

719228

show subpopulations

Gnomad4 AFR exome

AF:

0.0577

Gnomad4 AMR exome

AF:

0.232

Gnomad4 ASJ exome

AF:

0.232

Gnomad4 EAS exome

AF:

0.397

Gnomad4 SAS exome

AF:

0.395

Gnomad4 FIN exome

AF:

0.365

Gnomad4 NFE exome

AF:

0.356

Gnomad4 OTH exome

AF:

0.332

GnomAD4 genome

AF:

0.266

AC:

40448

AN:

152082

Hom.:

6630

Cov.:

AF XY:

0.269

AC XY:

19997

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0755

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.219

Gnomad4 EAS

AF:

0.424

Gnomad4 SAS

AF:

0.423

Gnomad4 FIN

AF:

0.358

Gnomad4 NFE

AF:

0.349

Gnomad4 OTH

AF:

0.261

Alfa

AF:

0.293

Hom.:

1291

Bravo

AF:

0.246

Asia WGS

AF:

0.387

AC:

1344

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 53% of patients studied by a panel of primary immunodeficiencies. Number of patients: 50. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 06, 2016	- -

Kabuki syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Kabuki syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Aug 23, 2018

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over