rs10496195

Positions:

• chr2-74847805-A-C
• chr2-74847805-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000189.5(HK2):​c.64-6488A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,172 control chromosomes in the GnomAD database, including 6,774 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 0.27 (6774 hom., cov: 32)
• Consequence: HK2 NM_000189.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HK2	NM_000189.5	c.64-6488A>C		intron_variant		ENST00000290573.7	NP_000180.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HK2	ENST00000290573.7	c.64-6488A>C		intron_variant		1	NM_000189.5	ENSP00000290573	P1
HK2	ENST00000409174.1	c.-21-6488A>C		intron_variant		1		ENSP00000387140

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41740 AN: 152052 Hom.: 6773 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.274 AC: 41750 AN: 152172 Hom.: 6774 Cov.: 32 AF XY: 0.270 AC XY: 20083 AN XY: 74390

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.307

Alfa AF: 0.349 Hom.: 13434

Bravo AF: 0.260

Asia WGS AF: 0.165 AC: 576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.044
DANN	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10496195; hg19: chr2-75074932;