rs200116899

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_003482.4(KMT2D):​c.2052T>G​(p.Pro684=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P684P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Consequence

KMT2D
NM_003482.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.289
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]

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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=-0.85).
BP7
Synonymous conserved (PhyloP=0.289 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KMT2DNM_003482.4 linkuse as main transcriptc.2052T>G p.Pro684= synonymous_variant 11/55 ENST00000301067.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KMT2DENST00000301067.12 linkuse as main transcriptc.2052T>G p.Pro684= synonymous_variant 11/555 NM_003482.4 A2O14686-1
KMT2DENST00000683543.2 linkuse as main transcriptc.2052T>G p.Pro684= synonymous_variant 11/56 P4
KMT2DENST00000685166.1 linkuse as main transcriptc.2052T>G p.Pro684= synonymous_variant 10/54 A2O14686-3
KMT2DENST00000692637.1 linkuse as main transcriptc.2052T>G p.Pro684= synonymous_variant 10/54 A2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
37
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
7.3
DANN
Benign
0.60
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-49445414; API