chr21-28858882-G-A

Variant names:

• chr21-28858882-G-A
• rs9985076
• XR_007067787.1:n.867+13731C>T

Variant summary

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

The XR_007067787.1(HEMK2):​n.867+13731C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0783 in 151,986 control chromosomes in the GnomAD database, including 1,112 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 0.078 (1112 hom., cov: 32)
• Consequence: HEMK2 XR_007067787.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	XR_007067787.1	n.867+13731C>T		intron_variant	Intron 7 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0782 AC: 11874 AN: 151868 Hom.: 1113 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0934

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.0721

Gnomad FIN AF: 0.00142

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00412

Gnomad OTH AF: 0.0541

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

GnomAD4 genome AF: 0.0783 AC: 11894 AN: 151986 Hom.: 1112 Cov.: 32 AF XY: 0.0784 AC XY: 5823 AN XY: 74306

African (AFR) AF: 0.212 AC: 8796 AN: 41422

American (AMR) AF: 0.0934 AC: 1425 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3472

East Asian (EAS) AF: 0.145 AC: 750 AN: 5178

South Asian (SAS) AF: 0.0717 AC: 345 AN: 4810

European-Finnish (FIN) AF: 0.00142 AC: 15 AN: 10564

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00412 AC: 280 AN: 67970

Other (OTH) AF: 0.0559 AC: 118 AN: 2112

Alfa AF: 0.0487 Hom.: 94

Bravo AF: 0.0918

Asia WGS AF: 0.112 AC: 389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.53
PhyloP100		0.44

Splicing

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

Other links and lift over

dbSNP: rs9985076; hg19: chr21-30231204;