rs680545

Positions:

• chr2-74848128-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HK2	NM_000189.5	c.64-6165G>A		intron_variant		ENST00000290573.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HK2	ENST00000290573.7	c.64-6165G>A		intron_variant		1	NM_000189.5	P1
HK2	ENST00000409174.1	c.-21-6165G>A		intron_variant		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

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.489

Alfa AF: 0.526 Hom.: 28656

Bravo AF: 0.472

Asia WGS AF: 0.299 AC: 1044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.85
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs680545; hg19: chr2-75075255;