Variant rs192659833 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003482.4(KMT2D):c.4401C>T(p.Gly1467=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,612,008 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 11 hom. )

Consequence

KMT2D
NM_003482.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.69

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=-0.81).

BP6

Variant 12-49046626-G-A is Benign according to our data. Variant chr12-49046626-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 281493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49046626-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-2.68 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00116 (177/152266) while in subpopulation EAS AF= 0.0166 (86/5180). AF 95% confidence interval is 0.0138. There are 0 homozygotes in gnomad4. There are 100 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 177 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KMT2D	NM_003482.4 linkuse as main transcript	c.4401C>T	p.Gly1467=	synonymous_variant	16/55	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.4401C>T	p.Gly1467=	synonymous_variant	16/55	5	NM_003482.4	ENSP00000301067	A2	O14686-1

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

179

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.0169

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00233

AC:

577

AN:

247860

Hom.:

AF XY:

0.00213

AC XY:

287

AN XY:

134430

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00260

Gnomad EAS exome

AF:

0.0224

Gnomad SAS exome

AF:

0.0000984

Gnomad FIN exome

AF:

0.000653

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00121

AC:

1760

AN:

1459742

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

864

AN XY:

725866

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00265

Gnomad4 EAS exome

AF:

0.0175

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.000900

Gnomad4 NFE exome

AF:

0.000756

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00116

AC:

177

AN:

152266

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.0166

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000941

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000930

Hom.:

Bravo

AF:

0.00132

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000771

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jun 16, 2015

- -

Kabuki syndrome 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

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

Nov 01, 2016

- -

Kabuki syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 31, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.3

DANN

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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