rs2832077

Variant names:

• chr21-28768699-G-A
• rs2832077
• ENST00000824757.1:n.57+3295C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-28768699-G-A
• chr21-28768699-G-C

Variant summary

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

The ENST00000824757.1(ENSG00000232855):​n.57+3295C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,842 control chromosomes in the GnomAD database, including 3,209 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 0.19 (3209 hom., cov: 31)
• Consequence: ENSG00000232855 ENST00000824757.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450
• Publications: 14 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000824757.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000232855	ENST00000824757.1		n.57+3295C>T		intron	N/A
	ENSG00000232855	ENST00000824758.1		n.147+3295C>T		intron	N/A
	ENSG00000232855	ENST00000824759.1		n.139+3295C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29345 AN: 151724 Hom.: 3206 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.193 AC: 29340 AN: 151842 Hom.: 3209 Cov.: 31 AF XY: 0.198 AC XY: 14665 AN XY: 74202

African (AFR) AF: 0.112 AC: 4631 AN: 41448

American (AMR) AF: 0.269 AC: 4097 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3468

East Asian (EAS) AF: 0.407 AC: 2080 AN: 5110

South Asian (SAS) AF: 0.214 AC: 1033 AN: 4818

European-Finnish (FIN) AF: 0.232 AC: 2440 AN: 10524

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13666 AN: 67918

Other (OTH) AF: 0.231 AC: 488 AN: 2108

Alfa AF: 0.202 Hom.: 15166

Bravo AF: 0.193

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.9
DANN	Benign	0.75
PhyloP100		-0.45

Splicing

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

Other links and lift over

dbSNP: rs2832077; hg19: chr21-30141021;