Genetic Variant EHMT2:c.2917-18T>C (chr6-31883457-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.470

Publications

105 publications found

Variant links:

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 links:

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

EHMT2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EHMT2	NM_006709.5	MANE Select	c.2917-18T>C	intron	N/A	NP_006700.3
EHMT2	NM_001363689.2		c.3088-18T>C	intron	N/A	NP_001350618.1	A2ABF9
EHMT2	NM_001289413.2		c.2986-18T>C	intron	N/A	NP_001276342.1	A2ABF8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EHMT2	ENST00000375537.9	TSL:1 MANE Select	c.2917-18T>C	intron	N/A	ENSP00000364687.4	Q96KQ7-1
EHMT2	ENST00000395728.7	TSL:1	c.3088-18T>C	intron	N/A	ENSP00000379078.3	A2ABF9
EHMT2	ENST00000962959.1		c.2917-18T>C	intron	N/A	ENSP00000633018.1

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

30699

AN:

152014

Hom.:

3253

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.183

AC:

42817

AN:

234268

AF XY:

0.184

show subpopulations

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 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.:

AF XY:

0.210

AC XY:

152027

AN XY:

723556

show subpopulations

African (AFR)

AF:

0.229

AC:

7622

AN:

33354

American (AMR)

AF:

0.0888

AC:

3911

AN:

44040

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

3365

AN:

26030

East Asian (EAS)

AF:

0.155

AC:

6114

AN:

39418

South Asian (SAS)

AF:

0.173

AC:

14791

AN:

85390

European-Finnish (FIN)

AF:

0.209

AC:

10881

AN:

51968

Middle Eastern (MID)

AF:

0.0967

AC:

557

AN:

5758

European-Non Finnish (NFE)

AF:

0.225

AC:

249861

AN:

1109198

Other (OTH)

AF:

0.207

AC:

12454

AN:

60160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

13366

26732

40097

53463

66829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8778

17556

26334

35112

43890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.202

AC:

30703

AN:

152132

Hom.:

3249

Cov.:

AF XY:

0.199

AC XY:

14814

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.220

AC:

9115

AN:

41494

American (AMR)

AF:

0.113

AC:

1733

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

430

AN:

3470

East Asian (EAS)

AF:

0.245

AC:

1269

AN:

5178

South Asian (SAS)

AF:

0.193

AC:

931

AN:

4820

European-Finnish (FIN)

AF:

0.214

AC:

2265

AN:

10600

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.211

AC:

14310

AN:

67952

Other (OTH)

AF:

0.181

AC:

383

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1306

2612

3918

5224

6530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.205

Hom.:

6970

Bravo

AF:

0.193

Asia WGS

AF:

0.160

AC:

556

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.74

(source)

DANN

Benign

0.57

PhyloP100

-0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over