6-31883845-C-T

Variant names:

• chr6-31883845-C-T
• rs61745377
• NM_006709.5:c.2877G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_006709.5(EHMT2):​c.2877G>A​(p.Thr959Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,613,944 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (8 hom., cov: 31)
  • Exomes 𝑓: 0.00068 (11 hom.)
• Consequence: EHMT2 NM_006709.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.18
• Publications: 2 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-AS1 (HGNC:39751): (EHMT2 and SLC44A4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.001).
• BP6: Variant 6-31883845-C-T is Benign according to our data. Variant chr6-31883845-C-T is described in ClinVar as Benign. ClinVar VariationId is 780615.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.18 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00624 (950/152156) while in subpopulation AFR AF = 0.0215 (893/41502). AF 95% confidence interval is 0.0203. There are 8 homozygotes in GnomAd4. There are 435 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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.2877G>A	p.Thr959Thr	synonymous	Exon 22 of 28	NP_006700.3
	EHMT2	NM_001363689.2		c.3048G>A	p.Thr1016Thr	synonymous	Exon 21 of 27	NP_001350618.1	A2ABF9
	EHMT2	NM_001289413.2		c.2946G>A	p.Thr982Thr	synonymous	Exon 20 of 26	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.2877G>A	p.Thr959Thr	synonymous	Exon 22 of 28	ENSP00000364687.4	Q96KQ7-1
	EHMT2	ENST00000395728.7	TSL:1	c.3048G>A	p.Thr1016Thr	synonymous	Exon 21 of 27	ENSP00000379078.3	A2ABF9
	EHMT2	ENST00000962959.1		c.2877G>A	p.Thr959Thr	synonymous	Exon 22 of 29	ENSP00000633018.1

Frequencies

GnomAD3 genomes AF: 0.00622 AC: 946 AN: 152038 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00154 AC: 386 AN: 251446 AF XY: 0.00118

Gnomad AFR exome AF: 0.0188

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000703

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000685 AC: 1001 AN: 1461788 Hom.: 11 Cov.: 32 AF XY: 0.000589 AC XY: 428 AN XY: 727208

African (AFR) AF: 0.0234 AC: 784 AN: 33480

American (AMR) AF: 0.00186 AC: 83 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5758

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1111956

Other (OTH) AF: 0.00164 AC: 99 AN: 60390

GnomAD4 genome AF: 0.00624 AC: 950 AN: 152156 Hom.: 8 Cov.: 31 AF XY: 0.00585 AC XY: 435 AN XY: 74390

African (AFR) AF: 0.0215 AC: 893 AN: 41502

American (AMR) AF: 0.00321 AC: 49 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67988

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00285 Hom.: 1

Bravo AF: 0.00738

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.13
DANN	Benign	0.87
PhyloP100		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs61745377; hg19: chr6-31851622;