rs781978013
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001197104.2(KMT2A):c.1522G>A(p.Glu508Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
KMT2A
NM_001197104.2 missense
NM_001197104.2 missense
Scores
1
5
13
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.35
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KMT2A. . Gene score misZ 6.2276 (greater than the threshold 3.09). Trascript score misZ 8.7715 (greater than threshold 3.09). GenCC has associacion of gene with Wiedemann-Steiner syndrome.
BP4
Computational evidence support a benign effect (MetaRNN=0.1835784).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KMT2A | NM_001197104.2 | c.1522G>A | p.Glu508Lys | missense_variant | 3/36 | ENST00000534358.8 | NP_001184033.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KMT2A | ENST00000534358.8 | c.1522G>A | p.Glu508Lys | missense_variant | 3/36 | 1 | NM_001197104.2 | ENSP00000436786.2 | ||
ENSG00000285827 | ENST00000648261.1 | c.292G>A | p.Glu98Lys | missense_variant | 3/7 | ENSP00000498126.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250918Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135656
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461884Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727242
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GnomAD4 genome Cov.: 31
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31
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
.;.;T;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;L;.;L
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N;N;N;.
REVEL
Benign
Sift
Uncertain
.;D;D;D;.
Sift4G
Benign
.;T;T;T;.
Polyphen
0.38, 0.36
.;.;B;B;.
Vest4
0.29, 0.23
MutPred
0.16
.;Gain of ubiquitination at E508 (P = 9e-04);Gain of ubiquitination at E508 (P = 9e-04);.;Gain of ubiquitination at E508 (P = 9e-04);
MVP
0.59
MPC
0.98
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at