rs7743807

Variant names:

• chr6-31886766-C-T
• rs7743807
• NM_006709.5:c.2241+9G>A

Variant summary

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

The NM_006709.5(EHMT2):​c.2241+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 1,614,166 control chromosomes in the GnomAD database, including 1,941 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 0.050 (267 hom., cov: 33)
  • Exomes 𝑓: 0.043 (1674 hom.)
• Consequence: EHMT2 NM_006709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHMT2	NM_006709.5	c.2241+9G>A		intron_variant	Intron 17 of 27	ENST00000375537.9	NP_006700.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHMT2	ENST00000375537.9	c.2241+9G>A		intron_variant	Intron 17 of 27	1	NM_006709.5	ENSP00000364687.4

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7630 AN: 152236 Hom.: 267 Cov.: 33

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00263

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0398

Gnomad OTH AF: 0.0487

GnomAD3 exomes AF: 0.0294 AC: 7385 AN: 251238 Hom.: 190 AF XY: 0.0273 AC XY: 3708 AN XY: 135770

Gnomad AFR exome AF: 0.0950

Gnomad AMR exome AF: 0.0351

Gnomad ASJ exome AF: 0.0121

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.00426

Gnomad NFE exome AF: 0.0368

Gnomad OTH exome AF: 0.0362

GnomAD4 exome AF: 0.0425 AC: 62162 AN: 1461812 Hom.: 1674 Cov.: 32 AF XY: 0.0405 AC XY: 29438 AN XY: 727210

Gnomad4 AFR exome AF: 0.0957

Gnomad4 AMR exome AF: 0.0370

Gnomad4 ASJ exome AF: 0.0134

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000383

Gnomad4 FIN exome AF: 0.00489

Gnomad4 NFE exome AF: 0.0486

Gnomad4 OTH exome AF: 0.0416

GnomAD4 genome AF: 0.0501 AC: 7638 AN: 152354 Hom.: 267 Cov.: 33 AF XY: 0.0472 AC XY: 3519 AN XY: 74506

Gnomad4 AFR AF: 0.0947

Gnomad4 AMR AF: 0.0513

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00263

Gnomad4 NFE AF: 0.0398

Gnomad4 OTH AF: 0.0482

Alfa AF: 0.0404 Hom.: 147

Bravo AF: 0.0575

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.0381

EpiControl AF: 0.0402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7743807; hg19: chr6-31854543;