rs587778449
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBS1BS2
The NM_003482.4(KMT2D):c.2250_2276delGCACCTGTCCCCCCGGCCTGAGGAGCC(p.His751_Pro759del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,603,084 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0054 ( 8 hom., cov: 31)
Exomes 𝑓: 0.00058 ( 3 hom. )
Consequence
KMT2D
NM_003482.4 disruptive_inframe_deletion
NM_003482.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.58
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_003482.4.
BP6
Variant 12-49051406-TGGCTCCTCAGGCCGGGGGGACAGGTGC-T is Benign according to our data. Variant chr12-49051406-TGGCTCCTCAGGCCGGGGGGACAGGTGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 134661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49051406-TGGCTCCTCAGGCCGGGGGGACAGGTGC-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00537 (769/143318) while in subpopulation AFR AF= 0.019 (722/38012). AF 95% confidence interval is 0.0178. There are 8 homozygotes in gnomad4. There are 362 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 769 AD gene.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| KMT2D | ENST00000301067.12 | c.2250_2276delGCACCTGTCCCCCCGGCCTGAGGAGCC | p.His751_Pro759del | disruptive_inframe_deletion | Exon 11 of 55 | 5 | NM_003482.4 | ENSP00000301067.7 | ||
| KMT2D | ENST00000683543.2 | c.2250_2276delGCACCTGTCCCCCCGGCCTGAGGAGCC | p.His751_Pro759del | disruptive_inframe_deletion | Exon 11 of 56 | ENSP00000506726.1 | ||||
| KMT2D | ENST00000685166.1 | c.2250_2276delGCACCTGTCCCCCCGGCCTGAGGAGCC | p.His751_Pro759del | disruptive_inframe_deletion | Exon 10 of 54 | ENSP00000509386.1 | ||||
| KMT2D | ENST00000692637.1 | c.2250_2276delGCACCTGTCCCCCCGGCCTGAGGAGCC | p.His751_Pro759del | disruptive_inframe_deletion | Exon 10 of 54 | ENSP00000509666.1 |
Frequencies
GnomAD3 genomes 0.00535 AC: 766AN: 143200Hom.: 8 Cov.: 31
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GnomAD3 exomes AF: 0.00128 AC: 309AN: 242168Hom.: 0 AF XY: 0.00101 AC XY: 134AN XY: 132466
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GnomAD4 exome AF: 0.000579 AC: 845AN: 1459766Hom.: 3 AF XY: 0.000549 AC XY: 399AN XY: 726154
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GnomAD4 genome 0.00537 AC: 769AN: 143318Hom.: 8 Cov.: 31 AF XY: 0.00516 AC XY: 362AN XY: 70210
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2Other:1
Sep 19, 2013
ITMI
Significance: not provided
Review Status: no classification provided
Collection Method: reference population
- -
May 30, 2017
Genetic Services Laboratory, University of Chicago
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Apr 13, 2016
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not provided Benign:2
Jun 15, 2020
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Sep 01, 2016
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Kabuki syndrome 1 Benign:1
May 28, 2019
Mendelics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Kabuki syndrome Benign:1
Feb 01, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at