6-31882754-T-A

Variant names:

• chr6-31882754-T-A
• NM_006709.5:c.3142A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006709.5(EHMT2):​c.3142A>T​(p.Met1048Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EHMT2 NM_006709.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.82

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHMT2	NM_006709.5	c.3142A>T	p.Met1048Leu	missense_variant	Exon 25 of 28	ENST00000375537.9	NP_006700.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHMT2	ENST00000375537.9	c.3142A>T	p.Met1048Leu	missense_variant	Exon 25 of 28	1	NM_006709.5	ENSP00000364687.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 19, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3142A>T (p.M1048L) alteration is located in exon 25 (coding exon 25) of the EHMT2 gene. This alteration results from a A to T substitution at nucleotide position 3142, causing the methionine (M) at amino acid position 1048 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	.;.;.;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Uncertain	0.31	D
MutationAssessor	Benign	1.8	.;.;.;L
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Pathogenic	0.67
Sift	Benign	0.031	D;D;D;D
Sift4G	Uncertain	0.023	D;D;D;D
Polyphen		0.14, 0.38, 0.52	.;B;B;P
Vest4		0.46
MutPred		0.56		.;Loss of sheet (P = 0.0817);.;.;
MVP		0.88
MPC		1.9
ClinPred		0.84	D
GERP RS		4.6
Varity_R		0.62
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-31850531;