Genetic Variant NM_006709.5:c.3560G>A (chr6-31880157-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006709.5(EHMT2):c.3560G>A(p.Ser1187Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,460,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

EHMT2
NM_006709.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.16

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15507466).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
EHMT2	NM_006709.5	MANE Select	c.3560G>A	p.Ser1187Asn	missense	Exon 28 of 28	NP_006700.3
EHMT2	NM_001363689.2		c.3731G>A	p.Ser1244Asn	missense	Exon 27 of 27	NP_001350618.1	A2ABF9
EHMT2	NM_001289413.2		c.3629G>A	p.Ser1210Asn	missense	Exon 26 of 26	NP_001276342.1	A2ABF8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EHMT2	ENST00000375537.9	TSL:1 MANE Select	c.3560G>A	p.Ser1187Asn	missense	Exon 28 of 28	ENSP00000364687.4	Q96KQ7-1
EHMT2	ENST00000395728.7	TSL:1	c.3731G>A	p.Ser1244Asn	missense	Exon 27 of 27	ENSP00000379078.3	A2ABF9
EHMT2	ENST00000962959.1		c.3683G>A	p.Ser1228Asn	missense	Exon 29 of 29	ENSP00000633018.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000326

AC:

AN:

245616

AF XY:

0.0000373

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000727

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1460690

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726658

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

1111988

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000592

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

Eigen

Benign

0.023

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.042

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.2

PhyloP100

3.2

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.5

REVEL

Benign

0.092

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.011

Polyphen

0.0030

Vest4

0.19

MutPred

0.17

Loss of glycosylation at S1210 (P = 0.0219)

MVP

0.71

MPC

0.88

ClinPred

0.21

GERP RS

4.6

Varity_R

0.83

gMVP

0.80

Mutation Taster

=69/31

polymorphism

(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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over