11-118503146-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001197104.2(KMT2A):c.7254C>T(p.Asn2418Asn) 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:5

Conservation

PhyloP100: -0.541

Publications

17 publications found

Variant links:

COSMIC-nc: COSV63283268

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 Gene-Disease associations (from GenCC):

Wiedemann-Steiner syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Illumina, Labcorp Genetics (formerly Invitae), ClinGen

KMT2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 158707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
KMT2A	NM_001197104.2 link	c.7254C>T	p.Asn2418Asn	synonymous_variant	Exon 27 of 36	ENST00000534358.8	NP_001184033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT2A	ENST00000534358.8 link	c.7254C>T	p.Asn2418Asn	synonymous_variant	Exon 27 of 36	1	NM_001197104.2	ENSP00000436786.2

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

GnomAD2 exomes

AF:

0.0574

AC:

14411

AN:

250876

AF XY:

0.0585

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 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

African (AFR)

AF:

0.121

AC:

4059

AN:

33474

American (AMR)

AF:

0.0302

AC:

1352

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0541

AC:

1414

AN:

26132

East Asian (EAS)

AF:

0.0303

AC:

1202

AN:

39700

South Asian (SAS)

AF:

0.0752

AC:

6486

AN:

86232

European-Finnish (FIN)

AF:

0.0655

AC:

3485

AN:

53172

Middle Eastern (MID)

AF:

0.0562

AC:

324

AN:

5768

European-Non Finnish (NFE)

AF:

0.0619

AC:

68809

AN:

1111800

Other (OTH)

AF:

0.0628

AC:

3790

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

4340

8680

13019

17359

21699

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2632

5264

7896

10528

13160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0730

AC:

11103

AN:

152074

Hom.:

531

Cov.:

AF XY:

0.0727

AC XY:

5404

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.120

AC:

4980

AN:

41442

American (AMR)

AF:

0.0369

AC:

563

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0473

AC:

164

AN:

3468

East Asian (EAS)

AF:

0.0210

AC:

109

AN:

5182

South Asian (SAS)

AF:

0.0670

AC:

323

AN:

4818

European-Finnish (FIN)

AF:

0.0818

AC:

864

AN:

10562

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0585

AC:

3979

AN:

68010

Other (OTH)

AF:

0.0501

AC:

106

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

511

1022

1534

2045

2556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0633

Hom.:

219

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 19, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.3

(source)

DANN

Benign

0.63

PhyloP100

-0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over