rs759803583
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_003482.4(KMT2D):c.11796_11813del(p.Gln3934_Gln3939del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000358 in 1,397,734 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000036 ( 0 hom. )
Consequence
KMT2D
NM_003482.4 inframe_deletion
NM_003482.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.66
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 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_003482.4.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KMT2D | NM_003482.4 | c.11796_11813del | p.Gln3934_Gln3939del | inframe_deletion | 40/55 | ENST00000301067.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.11796_11813del | p.Gln3934_Gln3939del | inframe_deletion | 40/55 | 5 | NM_003482.4 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000194 AC: 3AN: 154406Hom.: 0 AF XY: 0.0000246 AC XY: 2AN XY: 81450
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GnomAD4 exome AF: 0.00000358 AC: 5AN: 1397734Hom.: 0 AF XY: 0.00000435 AC XY: 3AN XY: 689390
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Kabuki syndrome 1 Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | Shaikh Laboratory, University of Colorado | Feb 04, 2015 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 26, 2019 | Reported in an individual with a clinical diagnosis of Kabuki syndrome (Van Laarhoven et al., 2015); In-frame deletion of 6 amino acids in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25972376) - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at