Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_000189.5(HK2):c.753T>C(p.Asp251Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,613,760 control chromosomes in the GnomAD database, including 42,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.30 ( 8487 hom., cov: 32)

Exomes 𝑓: 0.21 ( 34471 hom. )

Consequence

HK2
NM_000189.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.30

Publications

15 publications found

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]

HK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 2-74874327-T-C is Benign according to our data. Variant chr2-74874327-T-C is described in ClinVar as Benign. ClinVar VariationId is 3059165.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HK2	NM_000189.5	MANE Select	c.753T>C	p.Asp251Asp	synonymous	Exon 7 of 18	NP_000180.2
	HK2	NM_001371525.1		c.669T>C	p.Asp223Asp	synonymous	Exon 7 of 18	NP_001358454.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HK2	ENST00000290573.7	TSL:1 MANE Select	c.753T>C	p.Asp251Asp	synonymous	Exon 7 of 18	ENSP00000290573.2
	HK2	ENST00000409174.1	TSL:1	c.669T>C	p.Asp223Asp	synonymous	Exon 7 of 18	ENSP00000387140.1

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

44955

AN:

151878

Hom.:

8456

Cov.:

show subpopulations

Gnomad AFR

AF:

0.537

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.197

Gnomad OTH

AF:

0.260

GnomAD2 exomes

AF:

0.222

AC:

55851

AN:

251216

AF XY:

0.219

show subpopulations

Gnomad AFR exome

AF:

0.546

Gnomad AMR exome

AF:

0.155

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.304

Gnomad FIN exome

AF:

0.221

Gnomad NFE exome

AF:

0.192

Gnomad OTH exome

AF:

0.209

GnomAD4 exome

AF:

0.207

AC:

302233

AN:

1461764

Hom.:

34471

Cov.:

AF XY:

0.206

AC XY:

149710

AN XY:

727178

show subpopulations

African (AFR)

AF:

0.555

AC:

18585

AN:

33474

American (AMR)

AF:

0.161

AC:

7216

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

4086

AN:

26134

East Asian (EAS)

AF:

0.349

AC:

13848

AN:

39696

South Asian (SAS)

AF:

0.213

AC:

18361

AN:

86244

European-Finnish (FIN)

AF:

0.220

AC:

11741

AN:

53412

Middle Eastern (MID)

AF:

0.258

AC:

1487

AN:

5768

European-Non Finnish (NFE)

AF:

0.192

AC:

213752

AN:

1111928

Other (OTH)

AF:

0.218

AC:

13157

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

14001

28002

42002

56003

70004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7628

15256

22884

30512

38140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.296

AC:

45038

AN:

151996

Hom.:

8487

Cov.:

AF XY:

0.296

AC XY:

21986

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.538

AC:

22281

AN:

41418

American (AMR)

AF:

0.210

AC:

3208

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

525

AN:

3472

East Asian (EAS)

AF:

0.311

AC:

1593

AN:

5128

South Asian (SAS)

AF:

0.195

AC:

937

AN:

4812

European-Finnish (FIN)

AF:

0.224

AC:

2372

AN:

10592

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.197

AC:

13421

AN:

67970

Other (OTH)

AF:

0.260

AC:

550

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1456

2911

4367

5822

7278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.235

Hom.:

2602

Bravo

AF:

0.304

Asia WGS

AF:

0.266

AC:

924

AN:

3478

EpiCase

AF:

0.194

EpiControl

AF:

0.189

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

HK2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.66

(source)

DANN

Benign

0.32

PhyloP100

-2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs2229622

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over