rs7107305
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001197104.2(KMT2A):āc.5679A>Gā(p.Leu1893=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0569 in 1,610,442 control chromosomes in the GnomAD database, including 2,965 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.042 ( 185 hom., cov: 32)
Exomes š: 0.058 ( 2780 hom. )
Consequence
KMT2A
NM_001197104.2 synonymous
NM_001197104.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.980
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 11-118497950-A-G is Benign according to our data. Variant chr11-118497950-A-G is described in ClinVar as [Benign]. Clinvar id is 158705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-118497950-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.98 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0617 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KMT2A | NM_001197104.2 | c.5679A>G | p.Leu1893= | synonymous_variant | 21/36 | ENST00000534358.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2A | ENST00000534358.8 | c.5679A>G | p.Leu1893= | synonymous_variant | 21/36 | 1 | NM_001197104.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0416 AC: 6331AN: 152168Hom.: 185 Cov.: 32
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GnomAD3 exomes AF: 0.0495 AC: 12447AN: 251324Hom.: 396 AF XY: 0.0527 AC XY: 7157AN XY: 135830
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GnomAD4 exome AF: 0.0585 AC: 85252AN: 1458156Hom.: 2780 Cov.: 30 AF XY: 0.0594 AC XY: 43121AN XY: 725596
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GnomAD4 genome ? AF: 0.0416 AC: 6331AN: 152286Hom.: 185 Cov.: 32 AF XY: 0.0424 AC XY: 3161AN XY: 74468
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 19, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 10, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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