chr6-31896527-G-A

Variant names:

• chr6-31896527-G-A
• rs659445
• NM_006709.5:c.329-11C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006709.5(EHMT2):​c.329-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 1,611,146 control chromosomes in the GnomAD database, including 400,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.76 (44753 hom., cov: 32)
  • Exomes 𝑓: 0.69 (356213 hom.)
• Consequence: EHMT2 NM_006709.5 intron
• Scores: Splicing: ADA: 0.00002037
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.206
• Publications: 39 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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 6-31896527-G-A is Benign according to our data. Variant chr6-31896527-G-A is described in ClinVar as Benign. ClinVar VariationId is 1235703.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHMT2	NM_006709.5	c.329-11C>T		intron_variant	Intron 3 of 27	ENST00000375537.9	NP_006700.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHMT2	ENST00000375537.9	c.329-11C>T		intron_variant	Intron 3 of 27	1	NM_006709.5	ENSP00000364687.4

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115533 AN: 151936 Hom.: 44692 Cov.: 32

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.819

GnomAD2 exomes AF: 0.769 AC: 188576 AN: 245158 AF XY: 0.770

Gnomad AFR exome AF: 0.861

Gnomad AMR exome AF: 0.905

Gnomad ASJ exome AF: 0.863

Gnomad EAS exome AF: 0.812

Gnomad FIN exome AF: 0.670

Gnomad NFE exome AF: 0.687

Gnomad OTH exome AF: 0.769

GnomAD4 exome AF: 0.691 AC: 1008651 AN: 1459092 Hom.: 356213 Cov.: 68 AF XY: 0.699 AC XY: 507124 AN XY: 725758

African (AFR) AF: 0.859 AC: 28684 AN: 33408

American (AMR) AF: 0.900 AC: 40014 AN: 44476

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 22299 AN: 26002

East Asian (EAS) AF: 0.869 AC: 34499 AN: 39680

South Asian (SAS) AF: 0.883 AC: 76082 AN: 86192

European-Finnish (FIN) AF: 0.660 AC: 34513 AN: 52278

Middle Eastern (MID) AF: 0.906 AC: 5218 AN: 5758

European-Non Finnish (NFE) AF: 0.652 AC: 724149 AN: 1110974

Other (OTH) AF: 0.716 AC: 43193 AN: 60324

GnomAD4 genome AF: 0.761 AC: 115655 AN: 152054 Hom.: 44753 Cov.: 32 AF XY: 0.765 AC XY: 56896 AN XY: 74340

African (AFR) AF: 0.859 AC: 35628 AN: 41494

American (AMR) AF: 0.869 AC: 13278 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 2982 AN: 3468

East Asian (EAS) AF: 0.797 AC: 4110 AN: 5156

South Asian (SAS) AF: 0.877 AC: 4235 AN: 4830

European-Finnish (FIN) AF: 0.665 AC: 7032 AN: 10580

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45768 AN: 67924

Other (OTH) AF: 0.820 AC: 1734 AN: 2114

Alfa AF: 0.725 Hom.: 48453

Bravo AF: 0.780

Asia WGS AF: 0.880 AC: 3062 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 13, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.4
DANN	Benign	0.59
PhyloP100		0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.0
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: rs659445; hg19: chr6-31864304;