Variant chr2-74874327-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HK2	NM_000189.5 linkuse as main transcript	c.753T>C	p.Asp251Asp	synonymous_variant	7/18	ENST00000290573.7	NP_000180.2	P52789

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HK2	ENST00000290573.7 linkuse as main transcript	c.753T>C	p.Asp251Asp	synonymous_variant	7/18	1	NM_000189.5	ENSP00000290573.2		P52789
HK2	ENST00000409174.1 linkuse as main transcript	c.669T>C	p.Asp223Asp	synonymous_variant	7/18	1		ENSP00000387140.1		E9PB90

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

GnomAD3 exomes

AF:

0.222

AC:

55851

AN:

251216

Hom.:

7312

AF XY:

0.219

AC XY:

29741

AN XY:

135788

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 SAS exome

AF:

0.216

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

Gnomad4 AFR exome

AF:

0.555

Gnomad4 AMR exome

AF:

0.161

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.349

Gnomad4 SAS exome

AF:

0.213

Gnomad4 FIN exome

AF:

0.220

Gnomad4 NFE exome

AF:

0.192

Gnomad4 OTH exome

AF:

0.218

GnomAD4 genome

AF:

0.296

AC:

45038

AN:

151996

Hom.:

8487

Cov.:

AF XY:

0.296

AC XY:

21986

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.538

Gnomad4 AMR

AF:

0.210

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.311

Gnomad4 SAS

AF:

0.195

Gnomad4 FIN

AF:

0.224

Gnomad4 NFE

AF:

0.197

Gnomad4 OTH

AF:

0.260

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

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HK2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 23, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.66

DANN

Benign

0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over