chr2-25231099-C-G

Position:

• chr2-25231099-C-G

Variant summary

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

The NM_022552.5(DNMT3A):​c.*3180G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,280 control chromosomes in the GnomAD database, including 3,636 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 0.21 (3634 hom., cov: 32)
  • Exomes 𝑓: 0.17 (2 hom.)
• Consequence: DNMT3A NM_022552.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNMT3A	NM_022552.5	c.*3180G>C		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	ENST00000321117.10	c.*3180G>C		3_prime_UTR_variant	23/23	1	NM_022552.5	ENSP00000324375	P3
DNMT3A	ENST00000264709.7	c.*3180G>C		3_prime_UTR_variant	23/23	1		ENSP00000264709	P3

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31729 AN: 152032 Hom.: 3613 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.196

GnomAD4 exome AF: 0.169 AC: 22 AN: 130 Hom.: 2 Cov.: 0 AF XY: 0.167 AC XY: 17 AN XY: 102

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.209 AC: 31786 AN: 152150 Hom.: 3634 Cov.: 32 AF XY: 0.216 AC XY: 16089 AN XY: 74386

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.196

Alfa AF: 0.107 Hom.: 170

Bravo AF: 0.216

Asia WGS AF: 0.197 AC: 689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13420827; hg19: chr2-25453968;