12-49030882-TG-TGG

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

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 0.125
Variant links:
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: {Likely_benign=2, Benign=2, Uncertain_significance=1}.
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

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KMT2DNM_003482.4 linkc.13671+10dupC intron_variant Intron 41 of 54 ENST00000301067.12 NP_003473.3 O14686-1Q59FG6Q6PIA1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KMT2DENST00000301067.12 linkc.13671+10_13671+11insC intron_variant Intron 41 of 54 5 NM_003482.4 ENSP00000301067.7 O14686-1

Frequencies

GnomAD3 genomes
AF:
0.0143
AC:
2169
AN:
152176
Hom.:
56
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0492
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00608
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.000377
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.0115
GnomAD3 exomes
AF:
0.00362
AC:
897
AN:
247986
Hom.:
19
AF XY:
0.00247
AC XY:
333
AN XY:
134662
show subpopulations
Gnomad AFR exome
AF:
0.0498
Gnomad AMR exome
AF:
0.00267
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000167
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.000606
Gnomad NFE exome
AF:
0.000116
Gnomad OTH exome
AF:
0.00183
GnomAD4 exome
AF:
0.00146
AC:
2136
AN:
1461340
Hom.:
58
Cov.:
38
AF XY:
0.00127
AC XY:
924
AN XY:
726970
show subpopulations
Gnomad4 AFR exome
AF:
0.0502
Gnomad4 AMR exome
AF:
0.00318
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.000507
Gnomad4 NFE exome
AF:
0.000102
Gnomad4 OTH exome
AF:
0.00272
GnomAD4 genome
AF:
0.0143
AC:
2174
AN:
152294
Hom.:
56
Cov.:
32
AF XY:
0.0136
AC XY:
1016
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0492
Gnomad4 AMR
AF:
0.00608
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000377
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.0114
Bravo
AF:
0.0161
Asia WGS
AF:
0.00289
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
May 02, 2014
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Feb 08, 2013
Genetic Services Laboratory, University of Chicago
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Kabuki syndrome Benign:2
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Feb 01, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Kabuki syndrome 1 Uncertain:1
Nov 01, 2016
Center for Human Genetics, Inc, Center for Human Genetics, Inc
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:1
May 01, 2019
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147210845; hg19: chr12-49424665; API