rs112620957
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_003482.4(KMT2D):c.2798-7del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000612 in 1,594,394 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0032 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00034 ( 7 hom. )
Consequence
KMT2D
NM_003482.4 splice_region, splice_polypyrimidine_tract, intron
NM_003482.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.15
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 -16 ACMG points.
BP6
?
Variant 12-49050796-AG-A is Benign according to our data. Variant chr12-49050796-AG-A is described in ClinVar as [Likely_benign]. Clinvar id is 193865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49050796-AG-A is described in Lovd as [Likely_benign]. Variant chr12-49050796-AG-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00317 (482/152270) while in subpopulation AFR AF= 0.0107 (445/41526). AF 95% confidence interval is 0.00989. There are 4 homozygotes in gnomad4. There are 228 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 480 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KMT2D | NM_003482.4 | c.2798-7del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000301067.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.2798-7del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_003482.4 | A2 | |||
KMT2D | ENST00000683543.2 | c.2798-7del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | P4 | |||||
KMT2D | ENST00000685166.1 | c.2798-7del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | A2 | |||||
KMT2D | ENST00000692637.1 | c.2798-7del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00315 AC: 480AN: 152152Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.000811 AC: 193AN: 237966Hom.: 2 AF XY: 0.000609 AC XY: 79AN XY: 129806
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GnomAD4 exome AF: 0.000342 AC: 493AN: 1442124Hom.: 7 Cov.: 35 AF XY: 0.000322 AC XY: 230AN XY: 714818
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 16, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 10, 2014 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Kabuki syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 11, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Kabuki syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 27, 2020 | - - |
Computational scores
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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