rs2832010

Variant names:

• chr21-28738056-T-C
• rs2832010
• ENST00000824757.1:n.57+33938A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000824757.1(ENSG00000232855):​n.57+33938A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 151,970 control chromosomes in the GnomAD database, including 4,551 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 0.23 (4551 hom., cov: 32)
• Consequence: ENSG00000232855 ENST00000824757.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 1 publications found

Genes affected

ENSG00000232855 (HGNC:58104):

HEMK2 (HGNC:16021): (N-6 adenine-specific DNA methyltransferase 1) This gene encodes an N(6)-adenine-specific DNA methyltransferase. The encoded enzyme may be involved in the methylation of release factor I during translation termination. This enzyme is also involved in converting the arsenic metabolite monomethylarsonous acid to the less toxic dimethylarsonic acid. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 11. [provided by RefSeq, Mar 2023]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	XR_007067787.1	n.936+83849A>G		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000232855	ENST00000824757.1	n.57+33938A>G		intron_variant	Intron 1 of 8
ENSG00000232855	ENST00000824758.1	n.147+33938A>G		intron_variant	Intron 1 of 11
ENSG00000232855	ENST00000824759.1	n.139+33938A>G		intron_variant	Intron 1 of 8

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34626 AN: 151852 Hom.: 4549 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.228 AC: 34655 AN: 151970 Hom.: 4551 Cov.: 32 AF XY: 0.232 AC XY: 17233 AN XY: 74276

African (AFR) AF: 0.351 AC: 14540 AN: 41384

American (AMR) AF: 0.215 AC: 3288 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1305 AN: 5166

South Asian (SAS) AF: 0.279 AC: 1345 AN: 4828

European-Finnish (FIN) AF: 0.224 AC: 2364 AN: 10554

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10293 AN: 67974

Other (OTH) AF: 0.220 AC: 465 AN: 2114

Alfa AF: 0.208 Hom.: 510

Bravo AF: 0.229

Asia WGS AF: 0.292 AC: 1018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.1
DANN	Benign	0.79
PhyloP100		-0.021

Splicing

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

Other links and lift over

dbSNP: rs2832010; hg19: chr21-30110378;