rs680545

Variant names:

• chr2-74848128-G-A
• rs680545
• NM_000189.5:c.64-6165G>A

Variant summary

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

The NM_000189.5(HK2):​c.64-6165G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,980 control chromosomes in the GnomAD database, including 17,825 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 0.48 (17825 hom., cov: 31)
• Consequence: HK2 NM_000189.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170
• Publications: 8 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000189.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HK2	NM_000189.5	MANE Select	c.64-6165G>A		intron	N/A	NP_000180.2
	HK2	NM_001371525.1		c.-21-6165G>A		intron	N/A	NP_001358454.1	E9PB90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HK2	ENST00000290573.7	TSL:1 MANE Select	c.64-6165G>A		intron	N/A	ENSP00000290573.2	P52789
	HK2	ENST00000409174.1	TSL:1	c.-21-6165G>A		intron	N/A	ENSP00000387140.1	E9PB90
	HK2	ENST00000912519.1		c.64-6165G>A		intron	N/A	ENSP00000582578.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72470 AN: 151862 Hom.: 17821 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.477 AC: 72484 AN: 151980 Hom.: 17825 Cov.: 31 AF XY: 0.467 AC XY: 34704 AN XY: 74264

African (AFR) AF: 0.455 AC: 18841 AN: 41438

American (AMR) AF: 0.354 AC: 5416 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1887 AN: 3466

East Asian (EAS) AF: 0.288 AC: 1484 AN: 5160

South Asian (SAS) AF: 0.355 AC: 1713 AN: 4820

European-Finnish (FIN) AF: 0.435 AC: 4588 AN: 10556

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36911 AN: 67946

Other (OTH) AF: 0.489 AC: 1029 AN: 2106

Alfa AF: 0.520 Hom.: 38967

Bravo AF: 0.472

Asia WGS AF: 0.299 AC: 1044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.85
DANN	Benign	0.36
PhyloP100		0.017
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: rs680545; hg19: chr2-75075255;