GeneBe

12-49037507-ATGC-ATGCTGCTGC

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_003482.4(KMT2D):​c.9843_9848dupGCAGCA​(p.Gln3281_Gln3282dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,405,144 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KMT2D
NM_003482.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.79

Publications

0 publications found
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]
KMT2D Gene-Disease associations (from GenCC):
  • choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome
    Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Illumina, G2P
  • Kabuki syndrome 1
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Laboratory for Molecular Medicine, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • Kabuki syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_003482.4

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KMT2DNM_003482.4 linkc.9843_9848dupGCAGCA p.Gln3281_Gln3282dup disruptive_inframe_insertion Exon 35 of 55 ENST00000301067.12 NP_003473.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KMT2DENST00000301067.12 linkc.9843_9848dupGCAGCA p.Gln3281_Gln3282dup disruptive_inframe_insertion Exon 35 of 55 5 NM_003482.4 ENSP00000301067.7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000142
AC:
2
AN:
1405144
Hom.:
0
Cov.:
32
AF XY:
0.00000144
AC XY:
1
AN XY:
693652
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31842
American (AMR)
AF:
0.00
AC:
0
AN:
36088
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25230
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36088
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79726
European-Finnish (FIN)
AF:
0.0000202
AC:
1
AN:
49612
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5712
European-Non Finnish (NFE)
AF:
9.24e-7
AC:
1
AN:
1082430
Other (OTH)
AF:
0.00
AC:
0
AN:
58416
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.8

Splicing

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

Publications

Other links and lift over

dbSNP: rs758215754; hg19: chr12-49431290; API