chr21-28743805-T-G

Variant names:

• chr21-28743805-T-G
• rs2832042
• ENST00000824757.1:n.57+28189A>C

Variant summary

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

The ENST00000824757.1(ENSG00000232855):​n.57+28189A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,140 control chromosomes in the GnomAD database, including 4,624 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 (4624 hom., cov: 32)
• Consequence: ENSG00000232855 ENST00000824757.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	XR_007067787.1	n.936+78100A>C		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000232855	ENST00000824757.1	n.57+28189A>C		intron_variant	Intron 1 of 8
ENSG00000232855	ENST00000824758.1	n.147+28189A>C		intron_variant	Intron 1 of 11
ENSG00000232855	ENST00000824759.1	n.139+28189A>C		intron_variant	Intron 1 of 8

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34785 AN: 152022 Hom.: 4622 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.229 AC: 34813 AN: 152140 Hom.: 4624 Cov.: 32 AF XY: 0.233 AC XY: 17348 AN XY: 74422

African (AFR) AF: 0.353 AC: 14631 AN: 41472

American (AMR) AF: 0.216 AC: 3297 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3472

East Asian (EAS) AF: 0.254 AC: 1316 AN: 5174

South Asian (SAS) AF: 0.279 AC: 1346 AN: 4826

European-Finnish (FIN) AF: 0.226 AC: 2395 AN: 10598

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

European-Non Finnish (NFE) AF: 0.152 AC: 10309 AN: 68000

Other (OTH) AF: 0.219 AC: 464 AN: 2114

Alfa AF: 0.205 Hom.: 623

Bravo AF: 0.229

Asia WGS AF: 0.294 AC: 1023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.8
DANN	Benign	0.42
PhyloP100		0.0070

Splicing

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

Other links and lift over

dbSNP: rs2832042; hg19: chr21-30116127;