rs652888

Positions:

• chr6-31883457-A-G
• chr6-31883457-A-T

Variant summary

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

The NM_006709.5(EHMT2):​c.2917-18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,607,448 control chromosomes in the GnomAD database, including 38,123 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 0.20 (3249 hom., cov: 32)
  • Exomes 𝑓: 0.21 (34874 hom.)
• Consequence: EHMT2 NM_006709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470

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-AS1 (HGNC:39751): (EHMT2 and SLC44A4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EHMT2	NM_006709.5	c.2917-18T>C		intron_variant		ENST00000375537.9
EHMT2-AS1	NR_174947.1	n.1824A>G		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHMT2	ENST00000375537.9	c.2917-18T>C		intron_variant		1	NM_006709.5
EHMT2-AS1	ENST00000642849.1	n.1824A>G		non_coding_transcript_exon_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30699 AN: 152014 Hom.: 3253 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.182

GnomAD3 exomes AF: 0.183 AC: 42817 AN: 234268 Hom.: 4232 AF XY: 0.184 AC XY: 23581 AN XY: 127876

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.0845

Gnomad ASJ exome AF: 0.127

Gnomad EAS exome AF: 0.251

Gnomad SAS exome AF: 0.172

Gnomad FIN exome AF: 0.204

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.171

GnomAD4 exome AF: 0.213 AC: 309556 AN: 1455316 Hom.: 34874 Cov.: 34 AF XY: 0.210 AC XY: 152027 AN XY: 723556

Gnomad4 AFR exome AF: 0.229

Gnomad4 AMR exome AF: 0.0888

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.207

GnomAD4 genome AF: 0.202 AC: 30703 AN: 152132 Hom.: 3249 Cov.: 32 AF XY: 0.199 AC XY: 14814 AN XY: 74368

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.181

Alfa AF: 0.192 Hom.: 3394

Bravo AF: 0.193

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.74
DANN	Benign	0.57

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: rs652888; hg19: chr6-31851234;