19-35730714-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_014727.3(KMT2B):c.5284C>T(p.Arg1762Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1762H) has been classified as Uncertain significance.
Frequency
Consequence
NM_014727.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KMT2B | NM_014727.3 | c.5284C>T | p.Arg1762Cys | missense_variant | 26/37 | ENST00000420124.4 | |
KMT2B | XM_011527561.3 | c.5218C>T | p.Arg1740Cys | missense_variant | 26/37 | ||
KMT2B | XM_011527562.3 | c.5284C>T | p.Arg1762Cys | missense_variant | 26/36 | ||
KMT2B | XM_047439787.1 | c.5008C>T | p.Arg1670Cys | missense_variant | 25/36 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2B | ENST00000420124.4 | c.5284C>T | p.Arg1762Cys | missense_variant | 26/37 | 1 | NM_014727.3 | P2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Dystonia 28, childhood-onset Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | Apr 16, 2018 | This variant is interpreted as a Uncertain Significance, for Dystonia 28, childhood-onset, Autosomal Dominant inheritance. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM6 => Assumed de novo, but without confirmation of paternity and maternity (PMID:27992417). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at