rs2832057

Variant names:

• chr21-28760755-T-C
• rs2832057
• ENST00000824757.1:n.57+11239A>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+11239A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,142 control chromosomes in the GnomAD database, including 1,502 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 (1502 hom., cov: 33)
• Consequence: ENSG00000232855 ENST00000824757.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	XR_007067787.1	n.936+61150A>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+11239A>G		intron_variant	Intron 1 of 8
ENSG00000232855	ENST00000824758.1	n.147+11239A>G		intron_variant	Intron 1 of 11
ENSG00000232855	ENST00000824759.1	n.139+11239A>G		intron_variant	Intron 1 of 8

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20049 AN: 152024 Hom.: 1492 Cov.: 33

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0826

Gnomad FIN AF: 0.0767

Gnomad MID AF: 0.237

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: 0.132 AC: 20090 AN: 152142 Hom.: 1502 Cov.: 33 AF XY: 0.127 AC XY: 9456 AN XY: 74410

African (AFR) AF: 0.190 AC: 7878 AN: 41496

American (AMR) AF: 0.108 AC: 1644 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0922 AC: 320 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5178

South Asian (SAS) AF: 0.0831 AC: 401 AN: 4826

European-Finnish (FIN) AF: 0.0767 AC: 814 AN: 10606

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8611 AN: 67970

Other (OTH) AF: 0.131 AC: 277 AN: 2112

Alfa AF: 0.128 Hom.: 2175

Bravo AF: 0.134

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	11
DANN	Benign	0.70
PhyloP100		0.011

Splicing

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

Other links and lift over

dbSNP: rs2832057; hg19: chr21-30133077;