chr21-28849087-G-A

Variant names:

• chr21-28849087-G-A
• rs2832115
• XR_007067787.1:n.867+23526C>T

Variant summary

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

The XR_007067787.1(HEMK2):​n.867+23526C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,020 control chromosomes in the GnomAD database, including 6,584 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 0.27 (6584 hom., cov: 32)
• Consequence: HEMK2 XR_007067787.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.09
• Publications: 6 publications found

Genes affected

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=-1.08).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	XR_007067787.1	n.867+23526C>T		intron_variant	Intron 7 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41152 AN: 151902 Hom.: 6576 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.271 AC: 41192 AN: 152020 Hom.: 6584 Cov.: 32 AF XY: 0.273 AC XY: 20306 AN XY: 74298

African (AFR) AF: 0.438 AC: 18169 AN: 41448

American (AMR) AF: 0.247 AC: 3777 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 788 AN: 3472

East Asian (EAS) AF: 0.306 AC: 1585 AN: 5176

South Asian (SAS) AF: 0.299 AC: 1439 AN: 4814

European-Finnish (FIN) AF: 0.211 AC: 2230 AN: 10552

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12454 AN: 67976

Other (OTH) AF: 0.269 AC: 565 AN: 2104

Alfa AF: 0.214 Hom.: 11978

Bravo AF: 0.276

Asia WGS AF: 0.317 AC: 1100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.36
DANN	Benign	0.59
PhyloP100		-3.1

Splicing

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

Other links and lift over

dbSNP: rs2832115; hg19: chr21-30221409;