chr21-28736880-C-G

Variant names:

• chr21-28736880-C-G
• rs2251447
• ENST00000824757.1:n.57+35114G>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+35114G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,418 control chromosomes in the GnomAD database, including 4,721 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 (4721 hom., cov: 31)
• Consequence: ENSG00000232855 ENST00000824757.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	XR_007067787.1	n.936+85025G>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+35114G>C		intron_variant	Intron 1 of 8
ENSG00000232855	ENST00000824758.1	n.147+35114G>C		intron_variant	Intron 1 of 11
ENSG00000232855	ENST00000824759.1	n.139+35114G>C		intron_variant	Intron 1 of 8

Frequencies

GnomAD3 genomes AF: 0.231 AC: 34957 AN: 151332 Hom.: 4719 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.231 AC: 34985 AN: 151418 Hom.: 4721 Cov.: 31 AF XY: 0.235 AC XY: 17407 AN XY: 73948

African (AFR) AF: 0.361 AC: 14865 AN: 41226

American (AMR) AF: 0.217 AC: 3312 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 889 AN: 3468

East Asian (EAS) AF: 0.253 AC: 1299 AN: 5144

South Asian (SAS) AF: 0.279 AC: 1340 AN: 4798

European-Finnish (FIN) AF: 0.228 AC: 2353 AN: 10336

Middle Eastern (MID) AF: 0.208 AC: 60 AN: 288

European-Non Finnish (NFE) AF: 0.152 AC: 10296 AN: 67916

Other (OTH) AF: 0.222 AC: 467 AN: 2102

Alfa AF: 0.106 Hom.: 169

Bravo AF: 0.231

Asia WGS AF: 0.292 AC: 1016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.44
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs2251447; hg19: chr21-30109202;