rs7282280

Variant names:

• chr21-28842637-C-T
• rs7282280
• XR_007067787.1:n.868-20664G>A

Variant summary

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

The XR_007067787.1(HEMK2):​n.868-20664G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,096 control chromosomes in the GnomAD database, including 5,890 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 0.26 (5890 hom., cov: 32)
• Consequence: HEMK2 XR_007067787.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39439 AN: 151978 Hom.: 5884 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.260 AC: 39472 AN: 152096 Hom.: 5890 Cov.: 32 AF XY: 0.262 AC XY: 19455 AN XY: 74354

African (AFR) AF: 0.398 AC: 16521 AN: 41464

American (AMR) AF: 0.243 AC: 3716 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 788 AN: 3470

East Asian (EAS) AF: 0.307 AC: 1584 AN: 5166

South Asian (SAS) AF: 0.299 AC: 1441 AN: 4820

European-Finnish (FIN) AF: 0.210 AC: 2224 AN: 10582

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

European-Non Finnish (NFE) AF: 0.183 AC: 12461 AN: 67996

Other (OTH) AF: 0.261 AC: 552 AN: 2112

Alfa AF: 0.242 Hom.: 829

Bravo AF: 0.264

Asia WGS AF: 0.315 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.78
PhyloP100		-0.13

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7282280;

hg19: chr21-30214959;