rs9982426

Variant names:

• chr21-28835460-G-C
• rs9982426
• ENST00000824773.1:n.31+1277C>G

Your query was ambiguous. Multiple possible variants found:

• chr21-28835460-G-C
• chr21-28835460-G-T

Variant summary

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

The ENST00000824773.1(ENSG00000232855):​n.31+1277C>G 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 151,928 control chromosomes in the GnomAD database, including 5,877 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 (5877 hom., cov: 32)
• Consequence: ENSG00000232855 ENST00000824773.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	XR_007067787.1	n.868-13487C>G		intron_variant	Intron 7 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000232855	ENST00000824773.1	n.31+1277C>G		intron_variant	Intron 1 of 4
ENSG00000232855	ENST00000824774.1	n.50+1277C>G		intron_variant	Intron 1 of 3
ENSG00000232855	ENST00000824775.1	n.35+1277C>G		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39392 AN: 151810 Hom.: 5869 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.260 AC: 39429 AN: 151928 Hom.: 5877 Cov.: 32 AF XY: 0.262 AC XY: 19434 AN XY: 74276

African (AFR) AF: 0.399 AC: 16489 AN: 41372

American (AMR) AF: 0.243 AC: 3709 AN: 15258

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

East Asian (EAS) AF: 0.306 AC: 1581 AN: 5166

South Asian (SAS) AF: 0.300 AC: 1443 AN: 4816

European-Finnish (FIN) AF: 0.211 AC: 2227 AN: 10566

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

European-Non Finnish (NFE) AF: 0.183 AC: 12456 AN: 67970

Other (OTH) AF: 0.262 AC: 551 AN: 2106

Alfa AF: 0.110 Hom.: 172

Bravo AF: 0.264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.41
PhyloP100		-0.87

Splicing

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

Other links and lift over

dbSNP: rs9982426; hg19: chr21-30207782;