12-49051569-GAGTC-GGA
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_003482.4(KMT2D):c.2110_2113delinsTC(p.Asp704SerfsTer26) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. D704D) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
KMT2D
NM_003482.4 frameshift
NM_003482.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.13
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 Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 12-49051570-AGTC-GA is Pathogenic according to our data. Variant chr12-49051570-AGTC-GA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 547405.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KMT2D | NM_003482.4 | c.2110_2113delinsTC | p.Asp704SerfsTer26 | frameshift_variant | 11/55 | ENST00000301067.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.2110_2113delinsTC | p.Asp704SerfsTer26 | frameshift_variant | 11/55 | 5 | NM_003482.4 | A2 | |
KMT2D | ENST00000683543.2 | c.2110_2113delinsTC | p.Asp704SerfsTer26 | frameshift_variant | 11/56 | P4 | |||
KMT2D | ENST00000685166.1 | c.2110_2113delinsTC | p.Asp704SerfsTer26 | frameshift_variant | 10/54 | A2 | |||
KMT2D | ENST00000692637.1 | c.2110_2113delinsTC | p.Asp704SerfsTer26 | frameshift_variant | 10/54 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Kabuki syndrome 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at