12-49051742-TG-TGG
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_003482.4(KMT2D):c.1940dupC(p.Pro648ThrfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000268 in 1,119,960 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_003482.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.1940dupC | p.Pro648ThrfsTer2 | frameshift_variant | Exon 11 of 55 | 5 | NM_003482.4 | ENSP00000301067.7 | ||
KMT2D | ENST00000683543.2 | c.1940dupC | p.Pro648ThrfsTer2 | frameshift_variant | Exon 11 of 56 | ENSP00000506726.1 | ||||
KMT2D | ENST00000685166.1 | c.1940dupC | p.Pro648ThrfsTer2 | frameshift_variant | Exon 10 of 54 | ENSP00000509386.1 | ||||
KMT2D | ENST00000692637.1 | c.1940dupC | p.Pro648ThrfsTer2 | frameshift_variant | Exon 10 of 54 | ENSP00000509666.1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 95132Hom.: 0 Cov.: 28 FAILED QC
GnomAD4 exome AF: 0.00000195 AC: 2AN: 1024754Hom.: 0 Cov.: 35 AF XY: 0.00000194 AC XY: 1AN XY: 514562
GnomAD4 genome AF: 0.0000105 AC: 1AN: 95206Hom.: 0 Cov.: 28 AF XY: 0.0000219 AC XY: 1AN XY: 45592
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28475860, 35904121) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at