rs10496195

Variant names:

• chr2-74847805-A-C
• rs10496195
• NM_000189.5:c.64-6488A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-74847805-A-C
• chr2-74847805-A-G

Variant summary

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

The NM_000189.5(HK2):​c.64-6488A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,172 control chromosomes in the GnomAD database, including 6,774 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 0.27 (6774 hom., cov: 32)
• Consequence: HK2 NM_000189.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

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.64-6488A>C		intron	N/A	NP_000180.2
	HK2	NM_001371525.1		c.-21-6488A>C		intron	N/A	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.64-6488A>C		intron	N/A	ENSP00000290573.2	P52789
	HK2	ENST00000409174.1	TSL:1	c.-21-6488A>C		intron	N/A	ENSP00000387140.1	E9PB90
	HK2	ENST00000912519.1		c.64-6488A>C		intron	N/A	ENSP00000582578.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41740 AN: 152052 Hom.: 6773 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.274 AC: 41750 AN: 152172 Hom.: 6774 Cov.: 32 AF XY: 0.270 AC XY: 20083 AN XY: 74390

African (AFR) AF: 0.116 AC: 4812 AN: 41546

American (AMR) AF: 0.221 AC: 3384 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1123 AN: 3470

East Asian (EAS) AF: 0.144 AC: 745 AN: 5184

South Asian (SAS) AF: 0.182 AC: 877 AN: 4830

European-Finnish (FIN) AF: 0.338 AC: 3569 AN: 10572

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26045 AN: 67960

Other (OTH) AF: 0.307 AC: 649 AN: 2116

Alfa AF: 0.337 Hom.: 28764

Bravo AF: 0.260

Asia WGS AF: 0.165 AC: 576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.044
DANN	Benign	0.40
PhyloP100		-1.5
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: rs10496195; hg19: chr2-75074932;