chr6-31880443-T-G

Variant names:

• chr6-31880443-T-G
• rs589428
• NM_006709.5:c.3453-179A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363689.2(EHMT2):​c.3624-179A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 855,578 control chromosomes in the GnomAD database, including 223,934 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 0.77 (45946 hom., cov: 31)
  • Exomes 𝑓: 0.70 (177988 hom.)
• Consequence: EHMT2 NM_001363689.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 47 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363689.2. 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.3453-179A>C		intron	N/A	NP_006700.3
	EHMT2	NM_001363689.2		c.3624-179A>C		intron	N/A	NP_001350618.1
	EHMT2	NM_001289413.2		c.3522-179A>C		intron	N/A	NP_001276342.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHMT2	ENST00000375537.9	TSL:1 MANE Select	c.3453-179A>C		intron	N/A	ENSP00000364687.4
	EHMT2	ENST00000395728.7	TSL:1	c.3624-179A>C		intron	N/A	ENSP00000379078.3
	EHMT2	ENST00000962959.1		c.3576-179A>C		intron	N/A	ENSP00000633018.1

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116932 AN: 151992 Hom.: 45880 Cov.: 31

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.826

GnomAD4 exome AF: 0.703 AC: 494521 AN: 703468 Hom.: 177988 Cov.: 9 AF XY: 0.711 AC XY: 253416 AN XY: 356302

African (AFR) AF: 0.889 AC: 15057 AN: 16932

American (AMR) AF: 0.883 AC: 17029 AN: 19280

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 13058 AN: 15274

East Asian (EAS) AF: 0.878 AC: 28255 AN: 32170

South Asian (SAS) AF: 0.883 AC: 43983 AN: 49820

European-Finnish (FIN) AF: 0.657 AC: 20167 AN: 30696

Middle Eastern (MID) AF: 0.900 AC: 2227 AN: 2474

European-Non Finnish (NFE) AF: 0.656 AC: 329842 AN: 502554

Other (OTH) AF: 0.727 AC: 24903 AN: 34268

GnomAD4 genome AF: 0.770 AC: 117059 AN: 152110 Hom.: 45946 Cov.: 31 AF XY: 0.773 AC XY: 57508 AN XY: 74348

African (AFR) AF: 0.890 AC: 36938 AN: 41512

American (AMR) AF: 0.871 AC: 13310 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 2983 AN: 3470

East Asian (EAS) AF: 0.801 AC: 4133 AN: 5162

South Asian (SAS) AF: 0.877 AC: 4231 AN: 4822

European-Finnish (FIN) AF: 0.664 AC: 7024 AN: 10576

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45808 AN: 67970

Other (OTH) AF: 0.828 AC: 1743 AN: 2106

Alfa AF: 0.741 Hom.: 59343

Bravo AF: 0.790

Asia WGS AF: 0.888 AC: 3089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.45
DANN	Benign	0.54
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs589428; hg19: chr6-31848220;