rs6730141

Variant names:

• chr2-74858440-A-C
• rs6730141
• NM_000189.5:c.226+3985A>C

Variant summary

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

The NM_000189.5(HK2):​c.226+3985A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,990 control chromosomes in the GnomAD database, including 12,966 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 0.37 (12966 hom., cov: 32)
• Consequence: HK2 NM_000189.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.698
• Publications: 5 publications found

Genes affected

HK2 (HGNC:4923): (hexokinase 2) Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. This gene encodes hexokinase 2, the predominant form found in skeletal muscle. It localizes to the outer membrane of mitochondria. Expression of this gene is insulin-responsive, and studies in rat suggest that it is involved in the increased rate of glycolysis seen in rapidly growing cancer cells. [provided by RefSeq, Apr 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HK2	NM_000189.5	c.226+3985A>C		intron_variant	Intron 2 of 17	ENST00000290573.7	NP_000180.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HK2	ENST00000290573.7	c.226+3985A>C		intron_variant	Intron 2 of 17	1	NM_000189.5	ENSP00000290573.2
HK2	ENST00000409174.1	c.142+3985A>C		intron_variant	Intron 2 of 17	1		ENSP00000387140.1
HK2	ENST00000472302.1	n.123+3985A>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55775 AN: 151872 Hom.: 12919 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.368 AC: 55884 AN: 151990 Hom.: 12966 Cov.: 32 AF XY: 0.372 AC XY: 27608 AN XY: 74294

African (AFR) AF: 0.642 AC: 26599 AN: 41410

American (AMR) AF: 0.398 AC: 6081 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 498 AN: 3466

East Asian (EAS) AF: 0.510 AC: 2640 AN: 5172

South Asian (SAS) AF: 0.314 AC: 1512 AN: 4816

European-Finnish (FIN) AF: 0.300 AC: 3162 AN: 10544

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14500 AN: 67984

Other (OTH) AF: 0.313 AC: 661 AN: 2110

Alfa AF: 0.329 Hom.: 1819

Bravo AF: 0.389

Asia WGS AF: 0.446 AC: 1548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.7
DANN	Benign	0.39
PhyloP100		0.70
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: rs6730141; hg19: chr2-75085567;