rs7107305

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.5679A>G(p.Leu1893Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0569 in 1,610,442 control chromosomes in the GnomAD database, including 2,965 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 185 hom., cov: 32)

Exomes 𝑓: 0.058 ( 2780 hom. )

Consequence

KMT2A
NM_001197104.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.980

Publications

16 publications found

Variant links:

COSMIC-nc: COSV63283262

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=-0.54).

BP6

Variant 11-118497950-A-G is Benign according to our data. Variant chr11-118497950-A-G is described in ClinVar as Benign. ClinVar VariationId is 158705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.98 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2A	NM_001197104.2 link	c.5679A>G	p.Leu1893Leu	synonymous_variant	Exon 21 of 36	ENST00000534358.8	NP_001184033.1	Q03164-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT2A	ENST00000534358.8 link	c.5679A>G	p.Leu1893Leu	synonymous_variant	Exon 21 of 36	1	NM_001197104.2	ENSP00000436786.2		Q03164-3

Frequencies

GnomAD3 genomes

AF:

0.0416

AC:

6331

AN:

152168

Hom.:

185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0255

Gnomad ASJ

AF:

0.0473

Gnomad EAS

AF:

0.0210

Gnomad SAS

AF:

0.0672

Gnomad FIN

AF:

0.0816

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0584

Gnomad OTH

AF:

0.0345

GnomAD2 exomes

AF:

0.0495

AC:

12447

AN:

251324

AF XY:

0.0527

show subpopulations

Gnomad AFR exome

AF:

0.00953

Gnomad AMR exome

AF:

0.0225

Gnomad ASJ exome

AF:

0.0525

Gnomad EAS exome

AF:

0.0127

Gnomad FIN exome

AF:

0.0705

Gnomad NFE exome

AF:

0.0583

Gnomad OTH exome

AF:

0.0512

GnomAD4 exome

AF:

0.0585

AC:

85252

AN:

1458156

Hom.:

2780

Cov.:

AF XY:

0.0594

AC XY:

43121

AN XY:

725596

show subpopulations

African (AFR)

AF:

0.00864

AC:

289

AN:

33446

American (AMR)

AF:

0.0234

AC:

1046

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0541

AC:

1411

AN:

26096

East Asian (EAS)

AF:

0.0309

AC:

1227

AN:

39668

South Asian (SAS)

AF:

0.0754

AC:

6497

AN:

86138

European-Finnish (FIN)

AF:

0.0658

AC:

3513

AN:

53394

Middle Eastern (MID)

AF:

0.0501

AC:

289

AN:

5764

European-Non Finnish (NFE)

AF:

0.0610

AC:

67671

AN:

1108682

Other (OTH)

AF:

0.0549

AC:

3309

AN:

60258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

3519

7038

10558

14077

17596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2518

5036

7554

10072

12590

<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:

0.0416

AC:

6331

AN:

152286

Hom.:

185

Cov.:

AF XY:

0.0424

AC XY:

3161

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0102

AC:

425

AN:

41580

American (AMR)

AF:

0.0254

AC:

389

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0473

AC:

164

AN:

3468

East Asian (EAS)

AF:

0.0212

AC:

110

AN:

5184

South Asian (SAS)

AF:

0.0677

AC:

327

AN:

4830

European-Finnish (FIN)

AF:

0.0816

AC:

865

AN:

10600

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0584

AC:

3969

AN:

68010

Other (OTH)

AF:

0.0342

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

309

618

926

1235

1544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0510

Hom.:

174

Bravo

AF:

0.0363

Asia WGS

AF:

0.0400

AC:

138

AN:

3478

EpiCase

AF:

0.0563

EpiControl

AF:

0.0572

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Benign

Review Status:no assertion criteria provided

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

- -

not provided

Benign:3

Aug 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.9

(source)

DANN

Benign

0.76

PhyloP100

0.98

PromoterAI

0.012

Neutral

(source)

Mutation Taster

=100/0

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