NM_006709.5:c.711A>G

Variant names:

• chr6-31892560-T-C
• rs535586
• NM_006709.5:c.711A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006709.5(EHMT2):​c.711A>G​(p.Ser237Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 1,612,586 control chromosomes in the GnomAD database, including 404,034 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (45934 hom., cov: 31)
  • Exomes 𝑓: 0.69 (358100 hom.)
• Consequence: EHMT2 NM_006709.5 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.54
• Publications: 61 publications found

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]

EHMT2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-6.54 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHMT2	NM_006709.5	c.711A>G	p.Ser237Ser	splice_region_variant, synonymous_variant	Exon 7 of 28	ENST00000375537.9	NP_006700.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHMT2	ENST00000375537.9	c.711A>G	p.Ser237Ser	splice_region_variant, synonymous_variant	Exon 7 of 28	1	NM_006709.5	ENSP00000364687.4

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116910 AN: 151954 Hom.: 45868 Cov.: 31

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.825

GnomAD2 exomes AF: 0.772 AC: 190176 AN: 246328 AF XY: 0.772

Gnomad AFR exome AF: 0.895

Gnomad AMR exome AF: 0.906

Gnomad ASJ exome AF: 0.863

Gnomad EAS exome AF: 0.815

Gnomad FIN exome AF: 0.670

Gnomad NFE exome AF: 0.688

Gnomad OTH exome AF: 0.770

GnomAD4 exome AF: 0.693 AC: 1011486 AN: 1460514 Hom.: 358100 Cov.: 64 AF XY: 0.700 AC XY: 508528 AN XY: 726614

African (AFR) AF: 0.891 AC: 29794 AN: 33456

American (AMR) AF: 0.901 AC: 40273 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 22403 AN: 26124

East Asian (EAS) AF: 0.871 AC: 34577 AN: 39700

South Asian (SAS) AF: 0.883 AC: 76147 AN: 86250

European-Finnish (FIN) AF: 0.660 AC: 34528 AN: 52308

Middle Eastern (MID) AF: 0.906 AC: 5228 AN: 5768

European-Non Finnish (NFE) AF: 0.652 AC: 725186 AN: 1111850

Other (OTH) AF: 0.718 AC: 43350 AN: 60374

GnomAD4 genome AF: 0.770 AC: 117037 AN: 152072 Hom.: 45934 Cov.: 31 AF XY: 0.774 AC XY: 57490 AN XY: 74316

African (AFR) AF: 0.890 AC: 36933 AN: 41508

American (AMR) AF: 0.871 AC: 13313 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2983 AN: 3472

East Asian (EAS) AF: 0.800 AC: 4133 AN: 5164

South Asian (SAS) AF: 0.877 AC: 4229 AN: 4822

European-Finnish (FIN) AF: 0.664 AC: 7015 AN: 10560

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45795 AN: 67940

Other (OTH) AF: 0.826 AC: 1747 AN: 2114

Alfa AF: 0.721 Hom.: 76287

Bravo AF: 0.790

Asia WGS AF: 0.889 AC: 3092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.061
DANN	Benign	0.71
PhyloP100		-6.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs535586; hg19: chr6-31860337;