rs768264746

Variant names:

• chr2-74834606-A-C
• rs768264746
• NM_000189.5:c.26A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-74834606-A-C
• chr2-74834606-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000189.5(HK2):​c.26A>C​(p.Tyr9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000014 (0 hom.)
• Consequence: HK2 NM_000189.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.805

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HK2	NM_000189.5	c.26A>C	p.Tyr9Ser	missense_variant	Exon 1 of 18	ENST00000290573.7	NP_000180.2
HK2	XM_005264280.3	c.26A>C	p.Tyr9Ser	missense_variant	Exon 1 of 18		XP_005264337.1
HK2	XM_011532807.3	c.26A>C	p.Tyr9Ser	missense_variant	Exon 1 of 17		XP_011531109.1
HK2	XM_017003945.3	c.26A>C	p.Tyr9Ser	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.26A>C	p.Tyr9Ser	missense_variant	Exon 1 of 18	1	NM_000189.5	ENSP00000290573.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249656 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135128

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461632 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727162

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

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	Uncertain	0.55
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	26
DANN	Benign	0.96
DEOGEN2	Benign	0.35	T
Eigen	Benign	0.0076
Eigen_PC	Benign	0.040
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	0.31	D
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.56
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.045	D
Polyphen		0.70	P
Vest4		0.59
MutPred		0.71		Loss of stability (P = 0.0071);
MVP		0.92
MPC		0.59
ClinPred		0.37	T
GERP RS		2.8
Varity_R		0.23
gMVP		0.68

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

Other links and lift over

dbSNP: rs768264746; hg19: chr2-75061733;