Variant rs2276598 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_022552.5(DNMT3A):c.1266G>A(p.Leu422=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,612,420 control chromosomes in the GnomAD database, including 25,280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3635 hom., cov: 33)

Exomes 𝑓: 0.17 ( 21645 hom. )

Consequence

DNMT3A
NM_022552.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.673

Variant links:

Genes affected

DNMT3A (HGNC:2978): (DNA methyltransferase 3 alpha) CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase that is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes to the cytoplasm and nucleus and its expression is developmentally regulated. [provided by RefSeq, Mar 2016]

DNMT3A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 2-25246633-C-T is Benign according to our data. Variant chr2-25246633-C-T is described in ClinVar as [Benign]. Clinvar id is 1164958.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.673 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNMT3A	NM_022552.5 linkuse as main transcript	c.1266G>A	p.Leu422=	synonymous_variant	10/23	ENST00000321117.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNMT3A	ENST00000321117.10 linkuse as main transcript	c.1266G>A	p.Leu422=	synonymous_variant	10/23	1	NM_022552.5	P3	Q9Y6K1-1

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31799

AN:

152058

Hom.:

3622

Cov.:

show subpopulations

Gnomad AFR

AF:

0.292

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.316

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.181

GnomAD3 exomes

AF:

0.190

AC:

47115

AN:

247968

Hom.:

4890

AF XY:

0.183

AC XY:

24644

AN XY:

134780

show subpopulations

Gnomad AFR exome

AF:

0.295

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.196

Gnomad EAS exome

AF:

0.315

Gnomad SAS exome

AF:

0.117

Gnomad FIN exome

AF:

0.216

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.186

GnomAD4 exome

AF:

0.168

AC:

244632

AN:

1460242

Hom.:

21645

Cov.:

AF XY:

0.166

AC XY:

120277

AN XY:

726354

show subpopulations

Gnomad4 AFR exome

AF:

0.299

Gnomad4 AMR exome

AF:

0.202

Gnomad4 ASJ exome

AF:

0.198

Gnomad4 EAS exome

AF:

0.287

Gnomad4 SAS exome

AF:

0.119

Gnomad4 FIN exome

AF:

0.217

Gnomad4 NFE exome

AF:

0.158

Gnomad4 OTH exome

AF:

0.178

GnomAD4 genome

AF:

0.209

AC:

31839

AN:

152178

Hom.:

3635

Cov.:

AF XY:

0.211

AC XY:

15714

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.292

Gnomad4 AMR

AF:

0.178

Gnomad4 ASJ

AF:

0.191

Gnomad4 EAS

AF:

0.316

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.216

Gnomad4 NFE

AF:

0.165

Gnomad4 OTH

AF:

0.185

Alfa

AF:

0.183

Hom.:

1468

Bravo

AF:

0.212

Asia WGS

AF:

0.249

AC:

864

AN:

3478

EpiCase

AF:

0.160

EpiControl

AF:

0.164

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Tatton-Brown-Rahman overgrowth syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

6.9

DANN

Benign

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over