dbSNP rs7743807: EHMT2:c.2241+9G>A (chr6-31886766-C-T) – 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.2241+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 1,614,166 control chromosomes in the GnomAD database, including 1,941 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 0.050 ( 267 hom., cov: 33)

Exomes 𝑓: 0.043 ( 1674 hom. )

Consequence

EHMT2
NM_006709.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0290

Publications

15 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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

EHMT2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_006709.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0922 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.2241+9G>A	intron	N/A	NP_006700.3
EHMT2	NM_001363689.2		c.2412+9G>A	intron	N/A	NP_001350618.1	A2ABF9
EHMT2	NM_001289413.2		c.2310+9G>A	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.2241+9G>A	intron	N/A	ENSP00000364687.4	Q96KQ7-1
EHMT2	ENST00000395728.7	TSL:1	c.2412+9G>A	intron	N/A	ENSP00000379078.3	A2ABF9
EHMT2	ENST00000962959.1		c.2241+9G>A	intron	N/A	ENSP00000633018.1

Frequencies

GnomAD3 genomes

AF:

0.0501

AC:

7630

AN:

152236

Hom.:

267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0948

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0513

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00263

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0398

Gnomad OTH

AF:

0.0487

GnomAD2 exomes

AF:

0.0294

AC:

7385

AN:

251238

AF XY:

0.0273

show subpopulations

Gnomad AFR exome

AF:

0.0950

Gnomad AMR exome

AF:

0.0351

Gnomad ASJ exome

AF:

0.0121

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00426

Gnomad NFE exome

AF:

0.0368

Gnomad OTH exome

AF:

0.0362

GnomAD4 exome

AF:

0.0425

AC:

62162

AN:

1461812

Hom.:

1674

Cov.:

AF XY:

0.0405

AC XY:

29438

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.0957

AC:

3204

AN:

33478

American (AMR)

AF:

0.0370

AC:

1657

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0134

AC:

350

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39698

South Asian (SAS)

AF:

0.000383

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00489

AC:

261

AN:

53386

Middle Eastern (MID)

AF:

0.00798

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0486

AC:

54095

AN:

1111976

Other (OTH)

AF:

0.0416

AC:

2513

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

3911

7822

11732

15643

19554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2186

4372

6558

8744

10930

<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:

0.0501

AC:

7638

AN:

152354

Hom.:

267

Cov.:

AF XY:

0.0472

AC XY:

3519

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.0947

AC:

3937

AN:

41570

American (AMR)

AF:

0.0513

AC:

785

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000621

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00263

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0398

AC:

2705

AN:

68024

Other (OTH)

AF:

0.0482

AC:

102

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

377

754

1132

1509

1886

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0416

Hom.:

516

Bravo

AF:

0.0575

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.0381

EpiControl

AF:

0.0402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.8

(source)

DANN

Benign

0.59

PhyloP100

0.029

PromoterAI

0.0086

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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