rs2164411

Positions:

• chr2-25230037-G-A

Variant summary

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

The NM_022552.5(DNMT3A):​c.*4242C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,172 control chromosomes in the GnomAD database, including 2,910 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 0.18 (2910 hom., cov: 32)
  • Exomes 𝑓: 0.082 (0 hom.)
• Consequence: DNMT3A NM_022552.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNMT3A	NM_022552.5	c.*4242C>T		3_prime_UTR_variant	23/23	ENST00000321117.10	NP_072046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNMT3A	ENST00000321117	c.*4242C>T		3_prime_UTR_variant	23/23	1	NM_022552.5	ENSP00000324375.5
DNMT3A	ENST00000264709	c.*4242C>T		3_prime_UTR_variant	23/23	1		ENSP00000264709.3

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26916 AN: 151956 Hom.: 2897 Cov.: 32

Gnomad AFR AF: 0.0890

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.0816 AC: 8 AN: 98 Hom.: 0 Cov.: 0 AF XY: 0.0606 AC XY: 4 AN XY: 66

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.0833

Gnomad4 NFE exome AF: 0.0806

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.177 AC: 26939 AN: 152074 Hom.: 2910 Cov.: 32 AF XY: 0.186 AC XY: 13797 AN XY: 74312

Gnomad4 AFR AF: 0.0887

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.176

Alfa AF: 0.176 Hom.: 416

Bravo AF: 0.181

Asia WGS AF: 0.187 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.18
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2164411; hg19: chr2-25452906;