rs2205445

Variant names:

• chr21-28824690-T-C
• rs2205445
• ENST00000824773.1:n.32-2717A>G

Variant summary

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

The ENST00000824773.1(ENSG00000232855):​n.32-2717A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 152,272 control chromosomes in the GnomAD database, including 226 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 0.046 (226 hom., cov: 32)
• Consequence: ENSG00000232855 ENST00000824773.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	XR_007067787.1	n.868-2717A>G		intron_variant	Intron 7 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000232855	ENST00000824773.1	n.32-2717A>G		intron_variant	Intron 1 of 4
ENSG00000232855	ENST00000824774.1	n.51-2717A>G		intron_variant	Intron 1 of 3
ENSG00000232855	ENST00000824775.1	n.36-2717A>G		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.0463 AC: 7052 AN: 152154 Hom.: 224 Cov.: 32

Gnomad AFR AF: 0.0578

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0477

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0400

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0340

Gnomad OTH AF: 0.0487

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

GnomAD4 genome AF: 0.0464 AC: 7068 AN: 152272 Hom.: 226 Cov.: 32 AF XY: 0.0463 AC XY: 3449 AN XY: 74450

African (AFR) AF: 0.0577 AC: 2399 AN: 41542

American (AMR) AF: 0.0485 AC: 741 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3470

East Asian (EAS) AF: 0.157 AC: 811 AN: 5180

South Asian (SAS) AF: 0.0402 AC: 194 AN: 4822

European-Finnish (FIN) AF: 0.0120 AC: 127 AN: 10614

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0340 AC: 2315 AN: 68028

Other (OTH) AF: 0.0482 AC: 102 AN: 2116

Alfa AF: 0.0380 Hom.: 13

Bravo AF: 0.0515

Asia WGS AF: 0.0870 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.51
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs2205445; hg19: chr21-30197012;