Variant 11-118503146-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001197104.2(KMT2A):c.7254C>T(p.Asn2418=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0632 in 1,613,462 control chromosomes in the GnomAD database, including 3,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 531 hom., cov: 32)

Exomes 𝑓: 0.062 ( 3101 hom. )

Consequence

KMT2A
NM_001197104.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.541

Variant links:

Genes affected

KMT2A (HGNC:7132): (lysine methyltransferase 2A) This gene encodes a transcriptional coactivator that plays an essential role in regulating gene expression during early development and hematopoiesis. The encoded protein contains multiple conserved functional domains. One of these domains, the SET domain, is responsible for its histone H3 lysine 4 (H3K4) methyltransferase activity which mediates chromatin modifications associated with epigenetic transcriptional activation. This protein is processed by the enzyme Taspase 1 into two fragments, MLL-C and MLL-N. These fragments reassociate and further assemble into different multiprotein complexes that regulate the transcription of specific target genes, including many of the HOX genes. Multiple chromosomal translocations involving this gene are the cause of certain acute lymphoid leukemias and acute myeloid leukemias. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2010]

KMT2A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 11-118503146-C-T is Benign according to our data. Variant chr11-118503146-C-T is described in ClinVar as [Benign]. Clinvar id is 158707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-118503146-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.541 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMT2A	NM_001197104.2 linkuse as main transcript	c.7254C>T	p.Asn2418=	synonymous_variant	27/36	ENST00000534358.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMT2A	ENST00000534358.8 linkuse as main transcript	c.7254C>T	p.Asn2418=	synonymous_variant	27/36	1	NM_001197104.2	P4	Q03164-3

Frequencies

GnomAD3 genomes

AF:

0.0729

AC:

11077

AN:

151956

Hom.:

526

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0369

Gnomad ASJ

AF:

0.0473

Gnomad EAS

AF:

0.0208

Gnomad SAS

AF:

0.0666

Gnomad FIN

AF:

0.0818

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0585

Gnomad OTH

AF:

0.0507

GnomAD3 exomes

AF:

0.0574

AC:

14411

AN:

250876

Hom.:

508

AF XY:

0.0585

AC XY:

7931

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.117

Gnomad AMR exome

AF:

0.0286

Gnomad ASJ exome

AF:

0.0524

Gnomad EAS exome

AF:

0.0126

Gnomad SAS exome

AF:

0.0745

Gnomad FIN exome

AF:

0.0703

Gnomad NFE exome

AF:

0.0584

Gnomad OTH exome

AF:

0.0565

GnomAD4 exome

AF:

0.0622

AC:

90921

AN:

1461388

Hom.:

3101

Cov.:

AF XY:

0.0626

AC XY:

45505

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.0302

Gnomad4 ASJ exome

AF:

0.0541

Gnomad4 EAS exome

AF:

0.0303

Gnomad4 SAS exome

AF:

0.0752

Gnomad4 FIN exome

AF:

0.0655

Gnomad4 NFE exome

AF:

0.0619

Gnomad4 OTH exome

AF:

0.0628

GnomAD4 genome

AF:

0.0730

AC:

11103

AN:

152074

Hom.:

531

Cov.:

AF XY:

0.0727

AC XY:

5404

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.120

Gnomad4 AMR

AF:

0.0369

Gnomad4 ASJ

AF:

0.0473

Gnomad4 EAS

AF:

0.0210

Gnomad4 SAS

AF:

0.0670

Gnomad4 FIN

AF:

0.0818

Gnomad4 NFE

AF:

0.0585

Gnomad4 OTH

AF:

0.0501

Alfa

AF:

0.0627

Hom.:

189

Bravo

AF:

0.0734

Asia WGS

AF:

0.0470

AC:

162

AN:

3478

EpiCase

AF:

0.0565

EpiControl

AF:

0.0579

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Nov 19, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.3

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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