12-49051406-TGGCTCCTCAGGCCGGGGGGACAGGTGC-TGGCTCCTCAGGCCGGGGGGACAGGTGCGGCTCCTCAGGCCGGGGGGACAGGTGC
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4BS2
The NM_003482.4(KMT2D):c.2250_2276dupGCACCTGTCCCCCCGGCCTGAGGAGCC(p.Pro759_His760insHisLeuSerProArgProGluGluPro) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,603,008 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
KMT2D
NM_003482.4 disruptive_inframe_insertion
NM_003482.4 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.0500
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 Likely_benign. Variant got -2 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_003482.4.
BS2
High AC in GnomAdExome4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KMT2D | NM_003482.4 | c.2250_2276dupGCACCTGTCCCCCCGGCCTGAGGAGCC | p.Pro759_His760insHisLeuSerProArgProGluGluPro | disruptive_inframe_insertion | 11/55 | ENST00000301067.12 | NP_003473.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.2250_2276dupGCACCTGTCCCCCCGGCCTGAGGAGCC | p.Pro759_His760insHisLeuSerProArgProGluGluPro | disruptive_inframe_insertion | 11/55 | 5 | NM_003482.4 | ENSP00000301067.7 | ||
KMT2D | ENST00000683543.2 | c.2250_2276dupGCACCTGTCCCCCCGGCCTGAGGAGCC | p.Pro759_His760insHisLeuSerProArgProGluGluPro | disruptive_inframe_insertion | 11/56 | ENSP00000506726.1 | ||||
KMT2D | ENST00000685166.1 | c.2250_2276dupGCACCTGTCCCCCCGGCCTGAGGAGCC | p.Pro759_His760insHisLeuSerProArgProGluGluPro | disruptive_inframe_insertion | 10/54 | ENSP00000509386.1 | ||||
KMT2D | ENST00000692637.1 | c.2250_2276dupGCACCTGTCCCCCCGGCCTGAGGAGCC | p.Pro759_His760insHisLeuSerProArgProGluGluPro | disruptive_inframe_insertion | 10/54 | ENSP00000509666.1 |
Frequencies
GnomAD3 genomes AF: 0.0000209 AC: 3AN: 143218Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
3
AN:
143218
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: 0.0000206 AC: 5AN: 242168Hom.: 0 AF XY: 0.0000302 AC XY: 4AN XY: 132466
GnomAD3 exomes
AF:
AC:
5
AN:
242168
Hom.:
AF XY:
AC XY:
4
AN XY:
132466
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: 0.00000959 AC: 14AN: 1459790Hom.: 0 Cov.: 37 AF XY: 0.00000964 AC XY: 7AN XY: 726166
GnomAD4 exome
AF:
AC:
14
AN:
1459790
Hom.:
Cov.:
37
AF XY:
AC XY:
7
AN XY:
726166
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: 0.0000209 AC: 3AN: 143218Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 70096
GnomAD4 genome
AF:
AC:
3
AN:
143218
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
70096
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 07, 2021 | In-frame insertion of 9 amino acids in a non-repeat region; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at