rs486416

Positions:

• chr6-31888293-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006709.5(EHMT2):​c.1510-17C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 1,612,170 control chromosomes in the GnomAD database, including 400,806 homozygotes. 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 0.76 (44708 hom., cov: 33)
  • Exomes 𝑓: 0.69 (356098 hom.)
• Consequence: EHMT2 NM_006709.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHMT2	NM_006709.5	c.1510-17C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000375537.9	NP_006700.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHMT2	ENST00000375537.9	c.1510-17C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_006709.5	ENSP00000364687

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115507 AN: 152022 Hom.: 44647 Cov.: 33

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.818

GnomAD3 exomes AF: 0.769 AC: 188252 AN: 244664 Hom.: 73921 AF XY: 0.770 AC XY: 102771 AN XY: 133412

Gnomad AFR exome AF: 0.860

Gnomad AMR exome AF: 0.905

Gnomad ASJ exome AF: 0.863

Gnomad EAS exome AF: 0.812

Gnomad SAS exome AF: 0.883

Gnomad FIN exome AF: 0.669

Gnomad NFE exome AF: 0.687

Gnomad OTH exome AF: 0.770

GnomAD4 exome AF: 0.691 AC: 1008790 AN: 1460030 Hom.: 356098 Cov.: 60 AF XY: 0.698 AC XY: 507258 AN XY: 726300

Gnomad4 AFR exome AF: 0.858

Gnomad4 AMR exome AF: 0.900

Gnomad4 ASJ exome AF: 0.857

Gnomad4 EAS exome AF: 0.870

Gnomad4 SAS exome AF: 0.883

Gnomad4 FIN exome AF: 0.659

Gnomad4 NFE exome AF: 0.651

Gnomad4 OTH exome AF: 0.716

GnomAD4 genome AF: 0.760 AC: 115629 AN: 152140 Hom.: 44708 Cov.: 33 AF XY: 0.765 AC XY: 56869 AN XY: 74356

Gnomad4 AFR AF: 0.858

Gnomad4 AMR AF: 0.868

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.797

Gnomad4 SAS AF: 0.877

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.819

Alfa AF: 0.705 Hom.: 59425

Bravo AF: 0.780

Asia WGS AF: 0.880 AC: 3061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.72

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: rs486416; hg19: chr6-31856070;