6-31880443-T-G

Position:

• chr6-31880443-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006709.5(EHMT2):​c.3453-179A>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_006709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EHMT2	NM_006709.5	c.3453-179A>C		intron_variant		ENST00000375537.9
EHMT2-AS1	NR_174947.1	n.471T>G		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHMT2	ENST00000375537.9	c.3453-179A>C		intron_variant		1	NM_006709.5
EHMT2-AS1	ENST00000642849.1	n.471T>G		non_coding_transcript_exon_variant	2/5

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

Gnomad4 AFR exome AF: 0.889

Gnomad4 AMR exome AF: 0.883

Gnomad4 ASJ exome AF: 0.855

Gnomad4 EAS exome AF: 0.878

Gnomad4 SAS exome AF: 0.883

Gnomad4 FIN exome AF: 0.657

Gnomad4 NFE exome AF: 0.656

Gnomad4 OTH exome AF: 0.727

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

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.871

Gnomad4 ASJ AF: 0.860

Gnomad4 EAS AF: 0.801

Gnomad4 SAS AF: 0.877

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.828

Alfa AF: 0.727 Hom.: 30136

Bravo AF: 0.790

Asia WGS AF: 0.888 AC: 3089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.45
DANN	Benign	0.54

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

LitVar

Other links and lift over

dbSNP: rs589428; hg19: chr6-31848220;