rs556669370
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_003482.4(KMT2D):c.6126C>T(p.Cys2042=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,611,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
KMT2D
NM_003482.4 synonymous
NM_003482.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.63
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 Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP7
Synonymous conserved (PhyloP=1.63 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| KMT2D | NM_003482.4 | c.6126C>T | p.Cys2042= | synonymous_variant | 30/55 | ENST00000301067.12 | NP_003473.3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| KMT2D | ENST00000301067.12 | c.6126C>T | p.Cys2042= | synonymous_variant | 30/55 | 5 | NM_003482.4 | ENSP00000301067 | A2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000407 AC: 1AN: 245580Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133218
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GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459660Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 725938
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GnomAD4 genome 0.00000657 AC: 1AN: 152286Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74474
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Not reported inComputational scores
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Benign
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DANN
Benign
RBP_binding_hub_radar
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at