rs6730141

Positions:

• chr2-74858440-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000189.5(HK2):​c.226+3985A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,990 control chromosomes in the GnomAD database, including 12,966 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 0.37 (12966 hom., cov: 32)
• Consequence: HK2 NM_000189.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.698

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HK2	NM_000189.5	c.226+3985A>C		intron_variant		ENST00000290573.7	NP_000180.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HK2	ENST00000290573.7	c.226+3985A>C		intron_variant		1	NM_000189.5	ENSP00000290573	P1
HK2	ENST00000409174.1	c.142+3985A>C		intron_variant		1		ENSP00000387140
HK2	ENST00000472302.1	n.123+3985A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55775 AN: 151872 Hom.: 12919 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.368 AC: 55884 AN: 151990 Hom.: 12966 Cov.: 32 AF XY: 0.372 AC XY: 27608 AN XY: 74294

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.313

Alfa AF: 0.320 Hom.: 1649

Bravo AF: 0.389

Asia WGS AF: 0.446 AC: 1548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.7
DANN	Benign	0.39

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: rs6730141; hg19: chr2-75085567;