Genetic Variant NM_006709.5:c.1510-17C>T (chr6-31888293-G-A) – 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.140

Publications

42 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

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=-0.84).

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 rank	MANE	Protein	UniProt
EHMT2	NM_006709.5 link	c.1510-17C>T		intron_variant	Intron 12 of 27	ENST00000375537.9	NP_006700.3	Q96KQ7-1A0A024RCN9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHMT2	ENST00000375537.9 link	c.1510-17C>T		intron_variant	Intron 12 of 27	1	NM_006709.5	ENSP00000364687.4		Q96KQ7-1

Frequencies

GnomAD3 genomes

AF:

0.760

AC:

115507

AN:

152022

Hom.:

44647

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.698

AC XY:

507258

AN XY:

726300

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

20088

40175

60263

80350

100438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18958

37916

56874

75832

94790

<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:

0.760

AC:

115629

AN:

152140

Hom.:

44708

Cov.:

AF XY:

0.765

AC XY:

56869

AN XY:

74356

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1427

2855

4282

5710

7137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

856

1712

2568

3424

4280

<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:

0.721

Hom.:

112773

Bravo

AF:

0.780

Asia WGS

AF:

0.880

AC:

3061

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.2

(source)

DANN

Benign

0.72

PhyloP100

0.14

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over