rs2705671

Variant names:

• chr21-28879027-G-T
• rs2705671
• NM_013240.6:c.397-694C>A

Variant summary

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

The NM_013240.6(HEMK2):​c.397-694C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 146,190 control chromosomes in the GnomAD database, including 57,969 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 0.89 (57969 hom., cov: 28)
• Consequence: HEMK2 NM_013240.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	NM_013240.6	c.397-694C>A		intron_variant	Intron 4 of 5	ENST00000303775.10	NP_037372.4
HEMK2	NM_182749.5	c.313-694C>A		intron_variant	Intron 3 of 4		NP_877426.4
HEMK2	NR_047510.3	n.419-694C>A		intron_variant	Intron 4 of 6
HEMK2	XR_007067787.1	n.419-694C>A		intron_variant	Intron 4 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
N6AMT1	ENST00000303775.10	c.397-694C>A		intron_variant	Intron 4 of 5	1	NM_013240.6	ENSP00000303584.5
N6AMT1	ENST00000351429.7	c.313-694C>A		intron_variant	Intron 3 of 4	1		ENSP00000286764.4
N6AMT1	ENST00000460212.1	n.397-694C>A		intron_variant	Intron 4 of 6	1		ENSP00000436490.1

Frequencies

GnomAD3 genomes AF: 0.889 AC: 129921 AN: 146192 Hom.: 57964 Cov.: 28

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.822

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.875

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

GnomAD4 genome AF: 0.889 AC: 129928 AN: 146190 Hom.: 57969 Cov.: 28 AF XY: 0.888 AC XY: 62973 AN XY: 70924

African (AFR) AF: 0.933 AC: 37377 AN: 40070

American (AMR) AF: 0.820 AC: 11909 AN: 14518

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3088 AN: 3462

East Asian (EAS) AF: 0.662 AC: 3381 AN: 5104

South Asian (SAS) AF: 0.948 AC: 4523 AN: 4770

European-Finnish (FIN) AF: 0.910 AC: 7157 AN: 7864

Middle Eastern (MID) AF: 0.838 AC: 233 AN: 278

European-Non Finnish (NFE) AF: 0.888 AC: 59642 AN: 67174

Other (OTH) AF: 0.875 AC: 1786 AN: 2042

Alfa AF: 0.894 Hom.: 13539

Bravo AF: 0.879

Asia WGS AF: 0.817 AC: 2804 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.48
DANN	Benign	0.075
PhyloP100		-0.079
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2705671; hg19: chr21-30251349;