chr12-49026295-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_003482.4(KMT2D):c.15671G>A(p.Arg5224His) variant causes a missense change. The variant allele was found at a frequency of 0.000445 in 1,611,872 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R5224C) has been classified as Likely benign.
Frequency
Consequence
NM_003482.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KMT2D | NM_003482.4 | c.15671G>A | p.Arg5224His | missense_variant | 49/55 | ENST00000301067.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.15671G>A | p.Arg5224His | missense_variant | 49/55 | 5 | NM_003482.4 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000440 AC: 67AN: 152174Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000983 AC: 245AN: 249238Hom.: 1 AF XY: 0.000880 AC XY: 119AN XY: 135216
GnomAD4 exome AF: 0.000446 AC: 651AN: 1459580Hom.: 5 Cov.: 33 AF XY: 0.000419 AC XY: 304AN XY: 725530
GnomAD4 genome AF: 0.000440 AC: 67AN: 152292Hom.: 1 Cov.: 32 AF XY: 0.000497 AC XY: 37AN XY: 74460
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 02, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 09, 2020 | This variant is associated with the following publications: (PMID: 31935506, 30459467, 29707407) - |
Kabuki syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 04, 2013 | - - |
Kabuki syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 10, 2023 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at