chr21-28758655-G-A

Variant names:

• chr21-28758655-G-A
• rs2832053
• ENST00000824757.1:n.57+13339C>T

Variant summary

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

The ENST00000824757.1(ENSG00000232855):​n.57+13339C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,130 control chromosomes in the GnomAD database, including 1,832 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 0.15 (1832 hom., cov: 32)
• Consequence: ENSG00000232855 ENST00000824757.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	XR_007067787.1	n.936+63250C>T		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000232855	ENST00000824757.1	n.57+13339C>T		intron_variant	Intron 1 of 8
ENSG00000232855	ENST00000824758.1	n.147+13339C>T		intron_variant	Intron 1 of 11
ENSG00000232855	ENST00000824759.1	n.139+13339C>T		intron_variant	Intron 1 of 8

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22061 AN: 152012 Hom.: 1831 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.145 AC: 22061 AN: 152130 Hom.: 1832 Cov.: 32 AF XY: 0.152 AC XY: 11286 AN XY: 74380

African (AFR) AF: 0.158 AC: 6540 AN: 41506

American (AMR) AF: 0.170 AC: 2603 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 655 AN: 3464

East Asian (EAS) AF: 0.254 AC: 1315 AN: 5168

South Asian (SAS) AF: 0.216 AC: 1041 AN: 4816

European-Finnish (FIN) AF: 0.191 AC: 2022 AN: 10590

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7492 AN: 67986

Other (OTH) AF: 0.157 AC: 331 AN: 2110

Alfa AF: 0.135 Hom.: 194

Bravo AF: 0.140

Asia WGS AF: 0.258 AC: 899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.7
DANN	Benign	0.51
PhyloP100		0.38

Splicing

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

Other links and lift over

dbSNP: rs2832053; hg19: chr21-30130977;