chr12-49041037-G-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_003482.4(KMT2D):āc.6733C>Gā(p.Leu2245Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,567,318 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_003482.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KMT2D | NM_003482.4 | c.6733C>G | p.Leu2245Val | missense_variant | 32/55 | ENST00000301067.12 | NP_003473.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.6733C>G | p.Leu2245Val | missense_variant | 32/55 | 5 | NM_003482.4 | ENSP00000301067.7 |
Frequencies
GnomAD3 genomes AF: 0.00121 AC: 184AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00113 AC: 235AN: 208780Hom.: 0 AF XY: 0.00118 AC XY: 131AN XY: 111450
GnomAD4 exome AF: 0.00175 AC: 2475AN: 1415072Hom.: 1 Cov.: 35 AF XY: 0.00170 AC XY: 1189AN XY: 698900
GnomAD4 genome AF: 0.00121 AC: 184AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.00124 AC XY: 92AN XY: 74418
ClinVar
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 13, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 16, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 28, 2019 | This variant is associated with the following publications: (PMID: 29627316, 30459467, 30107592) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | KMT2D: BS1 - |
Kabuki syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Kabuki syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at