2-74834632-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000189.5(HK2):​c.52C>G​(p.Gln18Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HK2
NM_000189.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13922587).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HK2NM_000189.5 linkc.52C>G p.Gln18Glu missense_variant Exon 1 of 18 ENST00000290573.7 NP_000180.2 P52789
HK2XM_005264280.3 linkc.52C>G p.Gln18Glu missense_variant Exon 1 of 18 XP_005264337.1
HK2XM_011532807.3 linkc.52C>G p.Gln18Glu missense_variant Exon 1 of 17 XP_011531109.1
HK2XM_017003945.3 linkc.52C>G p.Gln18Glu missense_variant Exon 1 of 17 XP_016859434.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HK2ENST00000290573.7 linkc.52C>G p.Gln18Glu missense_variant Exon 1 of 18 1 NM_000189.5 ENSP00000290573.2 P52789

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152214
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249370
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134998
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461628
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727156
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152332
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.52C>G (p.Q18E) alteration is located in exon 1 (coding exon 1) of the HK2 gene. This alteration results from a C to G substitution at nucleotide position 52, causing the glutamine (Q) at amino acid position 18 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.046
T
BayesDel_noAF
Benign
-0.30
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.28
T
Eigen
Benign
0.15
Eigen_PC
Benign
0.21
FATHMM_MKL
Benign
0.69
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.061
D
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-0.82
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.50
N
REVEL
Benign
0.17
Sift
Benign
0.086
T
Sift4G
Benign
0.30
T
Polyphen
0.36
B
Vest4
0.39
MVP
0.68
MPC
0.44
ClinPred
0.59
D
GERP RS
4.1
Varity_R
0.39
gMVP
0.67

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201636455; hg19: chr2-75061759; API