chr6-31888293-G-A

Variant names:

• chr6-31888293-G-A
• rs486416
• NM_006709.5:c.1510-17C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006709.5(EHMT2):​c.1510-17C>T variant causes a 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 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 42 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006709.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHMT2	NM_006709.5	MANE Select	c.1510-17C>T		intron	N/A	NP_006700.3
	EHMT2	NM_001363689.2		c.1681-17C>T		intron	N/A	NP_001350618.1	A2ABF9
	EHMT2	NM_001289413.2		c.1579-17C>T		intron	N/A	NP_001276342.1	A2ABF8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHMT2	ENST00000375537.9	TSL:1 MANE Select	c.1510-17C>T		intron	N/A	ENSP00000364687.4	Q96KQ7-1
	EHMT2	ENST00000395728.7	TSL:1	c.1681-17C>T		intron	N/A	ENSP00000379078.3	A2ABF9
	EHMT2	ENST00000962959.1		c.1510-17C>T		intron	N/A	ENSP00000633018.1

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

GnomAD2 exomes AF: 0.769 AC: 188252 AN: 244664 AF XY: 0.770

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 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

African (AFR) AF: 0.858 AC: 28719 AN: 33478

American (AMR) AF: 0.900 AC: 40196 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 22333 AN: 26046

East Asian (EAS) AF: 0.870 AC: 34516 AN: 39694

South Asian (SAS) AF: 0.883 AC: 76098 AN: 86208

European-Finnish (FIN) AF: 0.659 AC: 34440 AN: 52250

Middle Eastern (MID) AF: 0.906 AC: 5221 AN: 5762

European-Non Finnish (NFE) AF: 0.651 AC: 724074 AN: 1111550

Other (OTH) AF: 0.716 AC: 43193 AN: 60360

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

African (AFR) AF: 0.858 AC: 35636 AN: 41522

American (AMR) AF: 0.868 AC: 13293 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2979 AN: 3470

East Asian (EAS) AF: 0.797 AC: 4116 AN: 5162

South Asian (SAS) AF: 0.877 AC: 4231 AN: 4824

European-Finnish (FIN) AF: 0.665 AC: 7038 AN: 10584

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.673 AC: 45721 AN: 67956

Other (OTH) AF: 0.819 AC: 1728 AN: 2110

Alfa AF: 0.721 Hom.: 112773

Bravo AF: 0.780

Asia WGS AF: 0.880 AC: 3061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.72
PhyloP100		0.14
Mutation Taster		=100/0	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: rs486416; hg19: chr6-31856070;