rs17745484

Variant names:

• chr2-25328261-C-T
• rs17745484
• NM_022552.5:c.-178+13565G>A

Variant summary

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

The NM_022552.5(DNMT3A):​c.-178+13565G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,102 control chromosomes in the GnomAD database, including 5,376 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 0.24 (5376 hom., cov: 32)
• Consequence: DNMT3A NM_022552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNMT3A	NM_022552.5	c.-178+13565G>A		intron_variant	Intron 1 of 22	ENST00000321117.10	NP_072046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNMT3A	ENST00000321117.10	c.-178+13565G>A		intron_variant	Intron 1 of 22	1	NM_022552.5	ENSP00000324375.5
DNMT3A	ENST00000264709.7	c.-177-14100G>A		intron_variant	Intron 1 of 22	1		ENSP00000264709.3
DNMT3A	ENST00000406659.3	c.-177-14100G>A		intron_variant	Intron 1 of 3	1		ENSP00000384852.3
DNMT3A	ENST00000380756.7	n.-177-14100G>A		intron_variant	Intron 1 of 23	1		ENSP00000370132.3

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36938 AN: 151984 Hom.: 5374 Cov.: 32

Gnomad AFR AF: 0.0872

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.243 AC: 36931 AN: 152102 Hom.: 5376 Cov.: 32 AF XY: 0.241 AC XY: 17892 AN XY: 74332

Gnomad4 AFR AF: 0.0871

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.263

Alfa AF: 0.314 Hom.: 5029

Bravo AF: 0.227

Asia WGS AF: 0.156 AC: 542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17745484; hg19: chr2-25551130;