21-28713624-G-T

Variant names:

• chr21-28713624-G-T
• rs2831972
• ENST00000824757.1:n.57+58370C>A

Variant summary

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

The ENST00000824757.1(ENSG00000232855):​n.57+58370C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,932 control chromosomes in the GnomAD database, including 23,881 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 0.54 (23881 hom., cov: 31)
• Consequence: ENSG00000232855 ENST00000824757.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	XR_007067787.1	n.936+108281C>A		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000232855	ENST00000824757.1	n.57+58370C>A		intron_variant	Intron 1 of 8
ENSG00000232855	ENST00000824758.1	n.147+58370C>A		intron_variant	Intron 1 of 11
ENSG00000232855	ENST00000824759.1	n.139+58370C>A		intron_variant	Intron 1 of 8

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81420 AN: 151810 Hom.: 23835 Cov.: 31

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.537 AC: 81520 AN: 151932 Hom.: 23881 Cov.: 31 AF XY: 0.537 AC XY: 39897 AN XY: 74230

African (AFR) AF: 0.755 AC: 31337 AN: 41486

American (AMR) AF: 0.551 AC: 8418 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1895 AN: 3466

East Asian (EAS) AF: 0.842 AC: 4330 AN: 5144

South Asian (SAS) AF: 0.436 AC: 2093 AN: 4800

European-Finnish (FIN) AF: 0.406 AC: 4281 AN: 10542

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.407 AC: 27637 AN: 67916

Other (OTH) AF: 0.542 AC: 1141 AN: 2106

Alfa AF: 0.497 Hom.: 2614

Bravo AF: 0.558

Asia WGS AF: 0.646 AC: 2246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.52
DANN	Benign	0.32
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs2831972; hg19: chr21-30085946;