rs2832070

Variant names:

• chr21-28765594-T-C
• rs2832070
• ENST00000824757.1:n.57+6400A>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+6400A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,134 control chromosomes in the GnomAD database, including 1,455 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 0.13 (1455 hom., cov: 32)
• Consequence: ENSG00000232855 ENST00000824757.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	XR_007067787.1	n.936+56311A>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+6400A>G		intron_variant	Intron 1 of 8
ENSG00000232855	ENST00000824758.1	n.147+6400A>G		intron_variant	Intron 1 of 11
ENSG00000232855	ENST00000824759.1	n.139+6400A>G		intron_variant	Intron 1 of 8

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19854 AN: 152016 Hom.: 1446 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0901

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0823

Gnomad FIN AF: 0.0861

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.131 AC: 19894 AN: 152134 Hom.: 1455 Cov.: 32 AF XY: 0.126 AC XY: 9394 AN XY: 74370

African (AFR) AF: 0.183 AC: 7618 AN: 41522

American (AMR) AF: 0.106 AC: 1623 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0901 AC: 312 AN: 3464

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5180

South Asian (SAS) AF: 0.0828 AC: 399 AN: 4818

European-Finnish (FIN) AF: 0.0861 AC: 913 AN: 10598

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8607 AN: 67956

Other (OTH) AF: 0.131 AC: 278 AN: 2116

Alfa AF: 0.124 Hom.: 731

Bravo AF: 0.132

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.64
PhyloP100		0.0040

Splicing

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

Other links and lift over

dbSNP: rs2832070; hg19: chr21-30137916;