chr6-31887640-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006709.5(EHMT2):​c.1948C>T​(p.His650Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

EHMT2
NM_006709.5 missense

Scores

3
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.57
Variant links:
Genes affected
EHMT2 (HGNC:14129): (euchromatic histone lysine methyltransferase 2) This gene encodes a methyltransferase that methylates lysine residues of histone H3. Methylation of H3 at lysine 9 by this protein results in recruitment of additional epigenetic regulators and repression of transcription. This gene was initially thought to be two different genes, NG36 and G9a, adjacent to each other in the HLA locus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31195188).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EHMT2NM_006709.5 linkuse as main transcriptc.1948C>T p.His650Tyr missense_variant 15/28 ENST00000375537.9 NP_006700.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EHMT2ENST00000375537.9 linkuse as main transcriptc.1948C>T p.His650Tyr missense_variant 15/281 NM_006709.5 ENSP00000364687 Q96KQ7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 16, 2024The c.1948C>T (p.H650Y) alteration is located in exon 15 (coding exon 15) of the EHMT2 gene. This alteration results from a C to T substitution at nucleotide position 1948, causing the histidine (H) at amino acid position 650 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Uncertain
0.062
T
BayesDel_noAF
Benign
-0.15
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.37
.;.;.;T
Eigen
Benign
0.12
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.31
T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Uncertain
2.3
.;.;.;M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-3.3
D;D;D;D
REVEL
Uncertain
0.32
Sift
Uncertain
0.0040
D;D;D;D
Sift4G
Uncertain
0.024
D;D;D;D
Polyphen
0.45, 0.24, 0.32
.;B;B;B
Vest4
0.47
MutPred
0.66
.;Loss of disorder (P = 0.0634);.;.;
MVP
0.72
MPC
1.4
ClinPred
0.95
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.20
gMVP
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1765051518; hg19: chr6-31855417; API