12-49030882-TG-TGG
Position:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_003482.4(KMT2D):c.13671+10dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,613,634 control chromosomes in the GnomAD database, including 114 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.014 ( 56 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 58 hom. )
Consequence
KMT2D
NM_003482.4 intron
NM_003482.4 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.125
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP6
Variant 12-49030882-T-TG is Benign according to our data. Variant chr12-49030882-T-TG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 94168.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2, Benign=2}.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2174/152294) while in subpopulation AFR AF= 0.0492 (2043/41560). AF 95% confidence interval is 0.0474. There are 56 homozygotes in gnomad4. There are 1016 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 2174 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0143 AC: 2169AN: 152176Hom.: 56 Cov.: 32
GnomAD3 genomes
AF:
AC:
2169
AN:
152176
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00362 AC: 897AN: 247986Hom.: 19 AF XY: 0.00247 AC XY: 333AN XY: 134662
GnomAD3 exomes
AF:
AC:
897
AN:
247986
Hom.:
AF XY:
AC XY:
333
AN XY:
134662
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00146 AC: 2136AN: 1461340Hom.: 58 Cov.: 38 AF XY: 0.00127 AC XY: 924AN XY: 726970
GnomAD4 exome
AF:
AC:
2136
AN:
1461340
Hom.:
Cov.:
38
AF XY:
AC XY:
924
AN XY:
726970
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0143 AC: 2174AN: 152294Hom.: 56 Cov.: 32 AF XY: 0.0136 AC XY: 1016AN XY: 74462
GnomAD4 genome
AF:
AC:
2174
AN:
152294
Hom.:
Cov.:
32
AF XY:
AC XY:
1016
AN XY:
74462
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
Asia WGS
AF:
AC:
11
AN:
3478
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Eurofins Ntd Llc (ga) | May 02, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Kabuki syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2024 | - - |
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 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 01, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at