6-31892560-T-C

Position:

• chr6-31892560-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006709.5(EHMT2):​c.711A>G​(p.Ser237=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
EHMT2	NM_006709.5	c.711A>G	p.Ser237=	splice_region_variant, synonymous_variant	7/28	ENST00000375537.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHMT2	ENST00000375537.9	c.711A>G	p.Ser237=	splice_region_variant, synonymous_variant	7/28	1	NM_006709.5

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

GnomAD3 exomes AF: 0.772 AC: 190176 AN: 246328 Hom.: 75014 AF XY: 0.772 AC XY: 103706 AN XY: 134280

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 SAS exome AF: 0.883

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

Gnomad4 AFR exome AF: 0.891

Gnomad4 AMR exome AF: 0.901

Gnomad4 ASJ exome AF: 0.858

Gnomad4 EAS exome AF: 0.871

Gnomad4 SAS exome AF: 0.883

Gnomad4 FIN exome AF: 0.660

Gnomad4 NFE exome AF: 0.652

Gnomad4 OTH exome AF: 0.718

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

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.871

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.877

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.826

Alfa AF: 0.722 Hom.: 16560

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
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

LitVar

Other links and lift over

dbSNP: rs535586; hg19: chr6-31860337;