2-74854341-G-A

Variant names:

• chr2-74854341-G-A
• NM_000189.5:c.112G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000189.5(HK2):​c.112G>A​(p.Glu38Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HK2 NM_000189.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HK2	NM_000189.5	MANE Select	c.112G>A	p.Glu38Lys	missense	Exon 2 of 18	NP_000180.2
	HK2	NM_001371525.1		c.28G>A	p.Glu10Lys	missense	Exon 2 of 18	NP_001358454.1	E9PB90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HK2	ENST00000290573.7	TSL:1 MANE Select	c.112G>A	p.Glu38Lys	missense	Exon 2 of 18	ENSP00000290573.2	P52789
	HK2	ENST00000409174.1	TSL:1	c.28G>A	p.Glu10Lys	missense	Exon 2 of 18	ENSP00000387140.1	E9PB90
	HK2	ENST00000912519.1		c.112G>A	p.Glu38Lys	missense	Exon 2 of 18	ENSP00000582578.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Uncertain	0.79	D
MutationAssessor	Benign	1.3	L
PhyloP100		9.6
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.58
Sift	Benign	0.36	T
Sift4G	Benign	0.49	T
Polyphen		0.31	B
Vest4		0.50
MutPred		0.50		Gain of MoRF binding (P = 0.0013)
MVP		0.92
MPC		0.50
ClinPred		0.91	D
GERP RS		5.1
Varity_R		0.65
gMVP		0.51
Mutation Taster		=51/49	polymorphism

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

Other links and lift over

hg19: chr2-75081468;