21-28628251-A-G

Variant names:

• chr21-28628251-A-G
• rs2831936
• ENST00000433310.6:n.203-1575T>C

Variant summary

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

The ENST00000433310.6(ENSG00000232855):​n.203-1575T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 152,190 control chromosomes in the GnomAD database, including 392 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 0.061 (392 hom., cov: 32)
• Consequence: ENSG00000232855 ENST00000433310.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	XR_007067787.1	n.937-50871T>C		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000232855	ENST00000433310.6	n.203-1575T>C		intron_variant	Intron 1 of 4	2
ENSG00000232855	ENST00000824757.1	n.58-1575T>C		intron_variant	Intron 1 of 8
ENSG00000232855	ENST00000824758.1	n.148-1575T>C		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.0611 AC: 9285 AN: 152072 Hom.: 391 Cov.: 32

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.0628

Gnomad ASJ AF: 0.0727

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0434

Gnomad FIN AF: 0.0452

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0943

Gnomad OTH AF: 0.0786

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

GnomAD4 genome AF: 0.0610 AC: 9285 AN: 152190 Hom.: 392 Cov.: 32 AF XY: 0.0580 AC XY: 4317 AN XY: 74388

African (AFR) AF: 0.0184 AC: 765 AN: 41552

American (AMR) AF: 0.0627 AC: 958 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0727 AC: 252 AN: 3468

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5182

South Asian (SAS) AF: 0.0437 AC: 211 AN: 4830

European-Finnish (FIN) AF: 0.0452 AC: 478 AN: 10578

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0943 AC: 6414 AN: 67994

Other (OTH) AF: 0.0787 AC: 166 AN: 2108

Alfa AF: 0.0795 Hom.: 84

Bravo AF: 0.0584

Asia WGS AF: 0.0220 AC: 77 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.47
DANN	Benign	0.76
PhyloP100		-0.29

Splicing

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

Other links and lift over

dbSNP: rs2831936; hg19: chr21-30000573;