rs745396055
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_003482.4(KMT2D):c.2785C>T(p.Leu929=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000578 in 1,384,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000058 ( 0 hom. )
Consequence
KMT2D
NM_003482.4 synonymous
NM_003482.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.97
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
Variant 12-49050898-G-A is Benign according to our data. Variant chr12-49050898-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 259056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=2.97 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KMT2D | NM_003482.4 | c.2785C>T | p.Leu929= | synonymous_variant | 11/55 | ENST00000301067.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.2785C>T | p.Leu929= | synonymous_variant | 11/55 | 5 | NM_003482.4 | A2 | |
KMT2D | ENST00000683543.2 | c.2785C>T | p.Leu929= | synonymous_variant | 11/56 | P4 | |||
KMT2D | ENST00000685166.1 | c.2785C>T | p.Leu929= | synonymous_variant | 10/54 | A2 | |||
KMT2D | ENST00000692637.1 | c.2785C>T | p.Leu929= | synonymous_variant | 10/54 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000155 AC: 3AN: 193134Hom.: 0 AF XY: 0.0000293 AC XY: 3AN XY: 102510
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GnomAD4 exome AF: 0.00000578 AC: 8AN: 1384800Hom.: 0 Cov.: 35 AF XY: 0.00000736 AC XY: 5AN XY: 679730
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Kabuki syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 02, 2022 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at