GeneBe

chr21-28842637-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XR_007067787.1(HEMK2):​n.868-20664G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,096 control chromosomes in the GnomAD database, including 5,890 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 0.26 ( 5890 hom., cov: 32)

Consequence

HEMK2
XR_007067787.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.134

Publications

5 publications found
Variant links:
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]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HEMK2XR_007067787.1 linkn.868-20664G>A intron_variant Intron 7 of 8

Ensembl

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

Frequencies

GnomAD3 genomes
AF:
0.260
AC:
39439
AN:
151978
Hom.:
5884
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.399
Gnomad AMI
AF:
0.130
Gnomad AMR
AF:
0.243
Gnomad ASJ
AF:
0.227
Gnomad EAS
AF:
0.306
Gnomad SAS
AF:
0.300
Gnomad FIN
AF:
0.210
Gnomad MID
AF:
0.225
Gnomad NFE
AF:
0.183
Gnomad OTH
AF:
0.261
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.260
AC:
39472
AN:
152096
Hom.:
5890
Cov.:
32
AF XY:
0.262
AC XY:
19455
AN XY:
74354
show subpopulations
African (AFR)
AF:
0.398
AC:
16521
AN:
41464
American (AMR)
AF:
0.243
AC:
3716
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.227
AC:
788
AN:
3470
East Asian (EAS)
AF:
0.307
AC:
1584
AN:
5166
South Asian (SAS)
AF:
0.299
AC:
1441
AN:
4820
European-Finnish (FIN)
AF:
0.210
AC:
2224
AN:
10582
Middle Eastern (MID)
AF:
0.224
AC:
66
AN:
294
European-Non Finnish (NFE)
AF:
0.183
AC:
12461
AN:
67996
Other (OTH)
AF:
0.261
AC:
552
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1463
2925
4388
5850
7313
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
388
776
1164
1552
1940
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.242
Hom.:
829
Bravo
AF:
0.264
Asia WGS
AF:
0.315
AC:
1095
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
1.7
DANN
Benign
0.78
PhyloP100
-0.13

Splicing

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

Publications

Other links and lift over

dbSNP: rs7282280; hg19: chr21-30214959; API