2-74847840-T-C

Variant names:

• chr2-74847840-T-C
• rs681900
• NM_000189.5:c.64-6453T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000189.5(HK2):​c.64-6453T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,168 control chromosomes in the GnomAD database, including 4,832 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4832 hom., cov: 33)
• Consequence: HK2 NM_000189.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HK2	NM_000189.5	c.64-6453T>C		intron_variant	Intron 1 of 17	ENST00000290573.7	NP_000180.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HK2	ENST00000290573.7	c.64-6453T>C		intron_variant	Intron 1 of 17	1	NM_000189.5	ENSP00000290573.2
HK2	ENST00000409174.1	c.-21-6453T>C		intron_variant	Intron 1 of 17	1		ENSP00000387140.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37259 AN: 152050 Hom.: 4834 Cov.: 33

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.234

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.245 AC: 37268 AN: 152168 Hom.: 4832 Cov.: 33 AF XY: 0.240 AC XY: 17865 AN XY: 74400

African (AFR) AF: 0.310 AC: 12875 AN: 41484

American (AMR) AF: 0.178 AC: 2724 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 912 AN: 3470

East Asian (EAS) AF: 0.151 AC: 780 AN: 5174

South Asian (SAS) AF: 0.193 AC: 930 AN: 4830

European-Finnish (FIN) AF: 0.180 AC: 1908 AN: 10604

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16517 AN: 67992

Other (OTH) AF: 0.232 AC: 490 AN: 2112

Alfa AF: 0.246 Hom.: 18507

Bravo AF: 0.249

Asia WGS AF: 0.146 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs681900; hg19: chr2-75074967;