Variant 7-152252613-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_ModerateBP6_Very_StrongBS2

The NM_170606.3(KMT2C):c.1402C>A(p.Pro468Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00131 in 1,613,302 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 2 hom. )

Consequence

KMT2C
NM_170606.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 5.71

Variant links:

Genes affected

KMT2C (HGNC:13726): (lysine methyltransferase 2C) This gene is a member of the myeloid/lymphoid or mixed-lineage leukemia (MLL) family and encodes a nuclear protein with an AT hook DNA-binding domain, a DHHC-type zinc finger, six PHD-type zinc fingers, a SET domain, a post-SET domain and a RING-type zinc finger. This protein is a member of the ASC-2/NCOA6 complex (ASCOM), which possesses histone methylation activity and is involved in transcriptional coactivation. [provided by RefSeq, Jul 2008]

KMT2C links:

KMT2C (HGNC:):

KMT2C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KMT2C. . Gene score misZ 2.1357 (greater than the threshold 3.09). Trascript score misZ 4.2875 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, syndromic intellectual disability, Kleefstra syndrome 2.

BP4

Computational evidence support a benign effect (MetaRNN=0.18792519).

BP6

Variant 7-152252613-G-T is Benign according to our data. Variant chr7-152252613-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 134737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 152 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KMT2C	NM_170606.3 linkuse as main transcript	c.1402C>A	p.Pro468Thr	missense_variant	10/59	ENST00000262189.11	NP_733751.2	Q8NEZ4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KMT2C	ENST00000262189.11 linkuse as main transcript	c.1402C>A	p.Pro468Thr	missense_variant	10/59	1	NM_170606.3	ENSP00000262189.6		Q8NEZ4-1

Frequencies

GnomAD3 genomes

AF:

0.000999

AC:

152

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00191

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000757

AC:

190

AN:

250888

Hom.:

AF XY:

0.000745

AC XY:

101

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000927

Gnomad NFE exome

AF:

0.00155

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.00134

AC:

1960

AN:

1460998

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

959

AN XY:

726832

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000937

Gnomad4 NFE exome

AF:

0.00170

Gnomad4 OTH exome

AF:

0.000795

GnomAD4 genome

AF:

0.000998

AC:

152

AN:

152304

Hom.:

Cov.:

AF XY:

0.000913

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00191

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00135

Hom.:

Bravo

AF:

0.000756

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.000857

AC:

104

EpiCase

AF:

0.00136

EpiControl

AF:

0.00166

ClinVar

Significance: Likely benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 08, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	KMT2C: BS1 -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Pathogenic

0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

T;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

.;D

M_CAP

Benign

0.060

MetaRNN

Benign

0.19

T;T

MetaSVM

Uncertain

0.15

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-4.3

D;D

REVEL

Uncertain

0.55

Sift

Uncertain

0.013

D;D

Polyphen

0.79

P;P

Vest4

0.91

MVP

0.79

MPC

0.28

ClinPred

0.073

GERP RS

6.0

Varity_R

0.18

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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