2-25255584-C-T

Position:

• chr2-25255584-C-T

Variant summary

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

The NM_022552.5(DNMT3A):​c.640-7332G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,036 control chromosomes in the GnomAD database, including 38,674 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 0.71 (38674 hom., cov: 31)
• Consequence: DNMT3A NM_022552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNMT3A	NM_022552.5	c.640-7332G>A		intron_variant		ENST00000321117.10	NP_072046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNMT3A	ENST00000321117.10	c.640-7332G>A		intron_variant		1	NM_022552.5	ENSP00000324375.5
DNMT3A	ENST00000264709.7	c.640-7332G>A		intron_variant		1		ENSP00000264709.3
DNMT3A	ENST00000380756.7	n.640-7332G>A		intron_variant		1		ENSP00000370132.3

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107727 AN: 151918 Hom.: 38641 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.697

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.709 AC: 107808 AN: 152036 Hom.: 38674 Cov.: 31 AF XY: 0.709 AC XY: 52676 AN XY: 74322

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.731

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.755

Gnomad4 OTH AF: 0.698

Alfa AF: 0.734 Hom.: 20724

Bravo AF: 0.702

Asia WGS AF: 0.619 AC: 2153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1465825; hg19: chr2-25478453;