rs960721516

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_014727.3(KMT2B):c.40G>A(p.Gly14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000517 in 986,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G14G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

KMT2B
NM_014727.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.256

Publications

2 publications found

Variant links:

Genes affected

KMT2B (HGNC:15840): (lysine methyltransferase 2B) This gene encodes a protein which contains multiple domains including a CXXC zinc finger, three PHD zinc fingers, two FY-rich domains, and a SET (suppressor of variegation, enhancer of zeste, and trithorax) domain. The SET domain is a conserved C-terminal domain that characterizes proteins of the MLL (mixed-lineage leukemia) family. This gene is ubiquitously expressed in adult tissues. It is also amplified in solid tumor cell lines, and may be involved in human cancer. Two alternatively spliced transcript variants encoding distinct isoforms have been reported for this gene, however, the full length nature of the shorter transcript is not known. [provided by RefSeq, Jul 2008]

KMT2B Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder with motor features
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
dystonia 28, childhood-onset
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
intellectual developmental disorder, autosomal dominant 68
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

KMT2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26403773).

BS2

High AC in GnomAdExome4 at 47 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014727.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KMT2B	NM_014727.3	MANE Select	c.40G>A	p.Gly14Ser	missense	Exon 1 of 37	NP_055542.1	Q9UMN6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KMT2B	ENST00000420124.4	TSL:1 MANE Select	c.40G>A	p.Gly14Ser	missense	Exon 1 of 37	ENSP00000398837.2	Q9UMN6
KMT2B	ENST00000673918.2		c.40G>A	p.Gly14Ser	missense	Exon 1 of 37	ENSP00000501283.1	A0A669KBI7
KMT2B	ENST00000687718.1		n.40G>A		non_coding_transcript_exon	Exon 1 of 3	ENSP00000510535.1	A0A8I5KWP7

Frequencies

GnomAD3 genomes

AF:

0.0000273

AC:

AN:

146512

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000456

Gnomad OTH

AF:

0.000495

GnomAD4 exome

AF:

0.0000559

AC:

AN:

840276

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

388872

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15878

American (AMR)

AF:

0.00

AC:

AN:

1242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5298

East Asian (EAS)

AF:

0.00

AC:

AN:

3856

South Asian (SAS)

AF:

0.00

AC:

AN:

17250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1644

European-Non Finnish (NFE)

AF:

0.0000587

AC:

AN:

766394

Other (OTH)

AF:

0.0000722

AC:

AN:

27710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000273

AC:

AN:

146512

Hom.:

Cov.:

AF XY:

0.0000281

AC XY:

AN XY:

71276

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40872

American (AMR)

AF:

0.00

AC:

AN:

14758

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3396

East Asian (EAS)

AF:

0.00

AC:

AN:

5132

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000456

AC:

AN:

65860

Other (OTH)

AF:

0.000495

AC:

AN:

2022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000453

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.025

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.51

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.0

PhyloP100

0.26

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.19

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.015

Polyphen

0.95

Vest4

0.28

MutPred

0.12

Gain of phosphorylation at G14 (P = 0.0028)

MVP

0.45

ClinPred

0.32

GERP RS

1.9

PromoterAI

0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.4

Varity_R

0.078

gMVP

0.11

Mutation Taster

=88/12

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over