rs55776396
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_003482.4(KMT2D):āc.15978T>Gā(p.Leu5326=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 1,613,796 control chromosomes in the GnomAD database, including 800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.025 ( 78 hom., cov: 32)
Exomes š: 0.029 ( 722 hom. )
Consequence
KMT2D
NM_003482.4 synonymous
NM_003482.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.10
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
Variant 12-49024652-A-C is Benign according to our data. Variant chr12-49024652-A-C is described in ClinVar as [Benign]. Clinvar id is 94189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49024652-A-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.1 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0251 (3822/152224) while in subpopulation NFE AF= 0.036 (2451/68016). AF 95% confidence interval is 0.0348. There are 78 homozygotes in gnomad4. There are 1874 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 3822 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KMT2D | NM_003482.4 | c.15978T>G | p.Leu5326= | synonymous_variant | 51/55 | ENST00000301067.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.15978T>G | p.Leu5326= | synonymous_variant | 51/55 | 5 | NM_003482.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0251 AC: 3824AN: 152106Hom.: 78 Cov.: 32
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GnomAD3 exomes AF: 0.0269 AC: 6691AN: 249048Hom.: 116 AF XY: 0.0273 AC XY: 3694AN XY: 135114
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GnomAD4 exome AF: 0.0290 AC: 42322AN: 1461572Hom.: 722 Cov.: 31 AF XY: 0.0289 AC XY: 21009AN XY: 727064
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GnomAD4 genome ? AF: 0.0251 AC: 3822AN: 152224Hom.: 78 Cov.: 32 AF XY: 0.0252 AC XY: 1874AN XY: 74442
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 20, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 06, 2012 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Kabuki syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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