rs2241726

Positions:

chr12-49050762-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003482.4(KMT2D):c.2826C>T(p.Ile942Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,609,518 control chromosomes in the GnomAD database, including 121,798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11787 hom., cov: 31)

Exomes 𝑓: 0.39 ( 110011 hom. )

Consequence

KMT2D
NM_003482.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.145

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 12-49050762-G-A is Benign according to our data. Variant chr12-49050762-G-A is described in ClinVar as [Benign]. Clinvar id is 94206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49050762-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.145 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 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.2826C>T	p.Ile942Ile	synonymous_variant	12/55	ENST00000301067.12	NP_003473.3	O14686-1Q59FG6Q6PIA1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KMT2D	ENST00000301067.12 linkuse as main transcript	c.2826C>T	p.Ile942Ile	synonymous_variant	12/55	5	NM_003482.4	ENSP00000301067.7	O14686-1
KMT2D	ENST00000683543.2 linkuse as main transcript	c.2826C>T	p.Ile942Ile	synonymous_variant	12/56			ENSP00000506726.1	A0A804HHR9
KMT2D	ENST00000685166.1 linkuse as main transcript	c.2826C>T	p.Ile942Ile	synonymous_variant	11/54			ENSP00000509386.1	O14686-3
KMT2D	ENST00000692637.1 linkuse as main transcript	c.2826C>T	p.Ile942Ile	synonymous_variant	11/54			ENSP00000509666.1	A0A8I5KSG1

Frequencies

GnomAD3 genomes

AF:

0.391

AC:

59288

AN:

151652

Hom.:

11760

Cov.:

show subpopulations

Gnomad AFR

AF:

0.424

Gnomad AMI

AF:

0.354

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.410

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.412

Gnomad MID

AF:

0.261

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.359

GnomAD3 exomes

AF:

0.375

AC:

92076

AN:

245850

Hom.:

17771

AF XY:

0.380

AC XY:

50810

AN XY:

133600

show subpopulations

Gnomad AFR exome

AF:

0.425

Gnomad AMR exome

AF:

0.266

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.422

Gnomad SAS exome

AF:

0.449

Gnomad FIN exome

AF:

0.413

Gnomad NFE exome

AF:

0.377

Gnomad OTH exome

AF:

0.362

GnomAD4 exome

AF:

0.386

AC:

562046

AN:

1457748

Hom.:

110011

Cov.:

AF XY:

0.387

AC XY:

280178

AN XY:

724438

show subpopulations

Gnomad4 AFR exome

AF:

0.429

Gnomad4 AMR exome

AF:

0.272

Gnomad4 ASJ exome

AF:

0.257

Gnomad4 EAS exome

AF:

0.377

Gnomad4 SAS exome

AF:

0.443

Gnomad4 FIN exome

AF:

0.412

Gnomad4 NFE exome

AF:

0.387

Gnomad4 OTH exome

AF:

0.383

GnomAD4 genome

AF:

0.391

AC:

59366

AN:

151770

Hom.:

11787

Cov.:

AF XY:

0.391

AC XY:

28986

AN XY:

74148

show subpopulations

Gnomad4 AFR

AF:

0.425

Gnomad4 AMR

AF:

0.327

Gnomad4 ASJ

AF:

0.248

Gnomad4 EAS

AF:

0.410

Gnomad4 SAS

AF:

0.464

Gnomad4 FIN

AF:

0.412

Gnomad4 NFE

AF:

0.385

Gnomad4 OTH

AF:

0.358

Alfa

AF:

0.369

Hom.:

11938

Bravo

AF:

0.380

Asia WGS

AF:

0.433

AC:

1504

AN:

3478

EpiCase

AF:

0.374

EpiControl

AF:

0.368

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 02, 2015	- -
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 57% of patients studied by a panel of primary immunodeficiencies. Number of patients: 54. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.5

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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