rs9332801

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.4284A>C(p.Ile1428Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0571 in 1,613,484 control chromosomes in the GnomAD database, including 2,973 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: 0.059 ( 2788 hom. )

Consequence

KMT2A
NM_001197104.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.77

Publications

17 publications found

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 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=-0.51).

BP6

Variant 11-118484927-A-C is Benign according to our data. Variant chr11-118484927-A-C is described in ClinVar as Benign. ClinVar VariationId is 158702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.77 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2A	NM_001197104.2 link	c.4284A>C	p.Ile1428Ile	synonymous_variant	Exon 10 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.4284A>C	p.Ile1428Ile	synonymous_variant	Exon 10 of 36	1	NM_001197104.2	ENSP00000436786.2

Frequencies

GnomAD3 genomes

AF:

0.0415

AC:

6321

AN:

152174

Hom.:

185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0255

Gnomad ASJ

AF:

0.0472

Gnomad EAS

AF:

0.0310

Gnomad SAS

AF:

0.0678

Gnomad FIN

AF:

0.0817

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0574

Gnomad OTH

AF:

0.0353

GnomAD2 exomes

AF:

0.0500

AC:

12569

AN:

251238

AF XY:

0.0532

show subpopulations

Gnomad AFR exome

AF:

0.00953

Gnomad AMR exome

AF:

0.0218

Gnomad ASJ exome

AF:

0.0526

Gnomad EAS exome

AF:

0.0234

Gnomad FIN exome

AF:

0.0702

Gnomad NFE exome

AF:

0.0577

Gnomad OTH exome

AF:

0.0514

GnomAD4 exome

AF:

0.0588

AC:

85866

AN:

1461192

Hom.:

2788

Cov.:

AF XY:

0.0598

AC XY:

43453

AN XY:

726904

show subpopulations

African (AFR)

AF:

0.00863

AC:

289

AN:

33472

American (AMR)

AF:

0.0229

AC:

1023

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.0541

AC:

1414

AN:

26126

East Asian (EAS)

AF:

0.0469

AC:

1860

AN:

39674

South Asian (SAS)

AF:

0.0763

AC:

6577

AN:

86190

European-Finnish (FIN)

AF:

0.0654

AC:

3496

AN:

53416

Middle Eastern (MID)

AF:

0.0512

AC:

295

AN:

5764

European-Non Finnish (NFE)

AF:

0.0608

AC:

67593

AN:

1111498

Other (OTH)

AF:

0.0550

AC:

3319

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

3807

7614

11421

15228

19035

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2530

5060

7590

10120

12650

<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:

0.0415

AC:

6321

AN:

152292

Hom.:

185

Cov.:

AF XY:

0.0426

AC XY:

3169

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0101

AC:

420

AN:

41582

American (AMR)

AF:

0.0254

AC:

389

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0472

AC:

164

AN:

3472

East Asian (EAS)

AF:

0.0312

AC:

162

AN:

5186

South Asian (SAS)

AF:

0.0683

AC:

329

AN:

4818

European-Finnish (FIN)

AF:

0.0817

AC:

866

AN:

10600

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0574

AC:

3907

AN:

68022

Other (OTH)

AF:

0.0350

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

320

641

961

1282

1602

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:

0.0517

Hom.:

306

Bravo

AF:

0.0363

Asia WGS

AF:

0.0430

AC:

150

AN:

3478

EpiCase

AF:

0.0559

EpiControl

AF:

0.0570

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

Significance:Benign

Review Status:no assertion criteria provided

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

- -

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

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.5

(source)

DANN

Benign

0.78

PhyloP100

1.8

PromoterAI

0.021

Neutral

(source)

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)

0.010

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