chr12-49040121-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003482.4(KMT2D):​c.7649C>T​(p.Pro2550Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

KMT2D
NM_003482.4 missense

Scores

2
9
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.96
Variant links:
Genes affected
KMT2D (HGNC:7133): (lysine methyltransferase 2D) The protein encoded by this gene is a histone methyltransferase that methylates the Lys-4 position of histone H3. The encoded protein is part of a large protein complex called ASCOM, which has been shown to be a transcriptional regulator of the beta-globin and estrogen receptor genes. Mutations in this gene have been shown to be a cause of Kabuki syndrome. [provided by RefSeq, Oct 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KMT2DNM_003482.4 linkc.7649C>T p.Pro2550Leu missense_variant 32/55 ENST00000301067.12 NP_003473.3 O14686-1Q59FG6Q6PIA1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KMT2DENST00000301067.12 linkc.7649C>T p.Pro2550Leu missense_variant 32/555 NM_003482.4 ENSP00000301067.7 O14686-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Uncertain
0.066
T
BayesDel_noAF
Benign
-0.14
CADD
Benign
22
DANN
Benign
0.94
DEOGEN2
Benign
0.24
T
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.83
T
M_CAP
Pathogenic
0.71
D
MetaRNN
Uncertain
0.64
D
MetaSVM
Uncertain
0.14
D
MutationAssessor
Benign
0.55
N
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-3.6
D
REVEL
Uncertain
0.48
Sift
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.45
MutPred
0.21
Loss of relative solvent accessibility (P = 0.0186);
MVP
0.43
MPC
0.65
ClinPred
0.76
D
GERP RS
4.8
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7
Varity_R
0.29
gMVP
0.11

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs368698254; hg19: chr12-49433904; API