Variant 2-74873281-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7

The ENST00000290573.7(HK2):c.501C>T(p.Phe167=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000337 in 1,612,806 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00037 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 1 hom. )

Consequence

HK2
ENST00000290573.7 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0440

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 2-74873281-C-T is Benign according to our data. Variant chr2-74873281-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3042674.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.044 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HK2	NM_000189.5 linkuse as main transcript	c.501C>T	p.Phe167=	synonymous_variant	5/18	ENST00000290573.7	NP_000180.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HK2	ENST00000290573.7 linkuse as main transcript	c.501C>T	p.Phe167=	synonymous_variant	5/18	1	NM_000189.5	ENSP00000290573	P1
HK2	ENST00000409174.1 linkuse as main transcript	c.417C>T	p.Phe139=	synonymous_variant	5/18	1		ENSP00000387140

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000558

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000414

AC:

104

AN:

251496

Hom.:

AF XY:

0.000493

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000545

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.000333

AC:

487

AN:

1460492

Hom.:

Cov.:

AF XY:

0.000354

AC XY:

257

AN XY:

726624

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000476

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000317

Gnomad4 OTH exome

AF:

0.000547

GnomAD4 genome

AF:

0.000368

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000472

Hom.:

Bravo

AF:

0.000280

EpiCase

AF:

0.000436

EpiControl

AF:

0.000948

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HK2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 25, 2019

This variant is classified as likely 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

-0.39

CADD

Benign

DANN

Benign

0.83

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