rs760644714

Variant names:

• chr2-74834635-G-A
• NM_000189.5:c.55G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-74834635-G-A
• chr2-74834635-G-C
• chr2-74834635-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000189.5(HK2):​c.55G>A​(p.Val19Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,642 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HK2 NM_000189.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.39

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31869465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HK2	NM_000189.5	c.55G>A	p.Val19Met	missense_variant	Exon 1 of 18	ENST00000290573.7	NP_000180.2
HK2	XM_005264280.3	c.55G>A	p.Val19Met	missense_variant	Exon 1 of 18		XP_005264337.1
HK2	XM_011532807.3	c.55G>A	p.Val19Met	missense_variant	Exon 1 of 17		XP_011531109.1
HK2	XM_017003945.3	c.55G>A	p.Val19Met	missense_variant	Exon 1 of 17		XP_016859434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HK2	ENST00000290573.7	c.55G>A	p.Val19Met	missense_variant	Exon 1 of 18	1	NM_000189.5	ENSP00000290573.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461642 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727160

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: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.094
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.051	T
Polyphen		0.92	P
Vest4		0.34
MutPred		0.52		Gain of helix (P = 0.0199);
MVP		0.65
MPC		0.41
ClinPred		0.81	D
GERP RS		4.3
Varity_R		0.21
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-75061762; COSMIC: COSV51874590; COSMIC: COSV51874590;