chr2-74873281-C-T

Variant names:

• chr2-74873281-C-T
• rs138918973
• NM_000189.5:c.501C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6 BP7

The NM_000189.5(HK2):​c.501C>T​(p.Phe167Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000337 in 1,612,806 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00037 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (1 hom.)
• Consequence: HK2 NM_000189.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0440
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 2-74873281-C-T is Benign according to our data. Variant chr2-74873281-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3042674.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.044 with no splicing effect.

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.501C>T	p.Phe167Phe	synonymous	Exon 5 of 18	NP_000180.2
	HK2	NM_001371525.1		c.417C>T	p.Phe139Phe	synonymous	Exon 5 of 18	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.501C>T	p.Phe167Phe	synonymous	Exon 5 of 18	ENSP00000290573.2	P52789
	HK2	ENST00000409174.1	TSL:1	c.417C>T	p.Phe139Phe	synonymous	Exon 5 of 18	ENSP00000387140.1	E9PB90
	HK2	ENST00000912519.1		c.501C>T	p.Phe167Phe	synonymous	Exon 5 of 18	ENSP00000582578.1

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 56 AN: 152196 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000558

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000414 AC: 104 AN: 251496 AF XY: 0.000493

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000636

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000545

Gnomad OTH exome AF: 0.000651

GnomAD4 exome AF: 0.000333 AC: 487 AN: 1460492 Hom.: 1 Cov.: 30 AF XY: 0.000354 AC XY: 257 AN XY: 726624

African (AFR) AF: 0.0000598 AC: 2 AN: 33446

American (AMR) AF: 0.000626 AC: 28 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.000476 AC: 41 AN: 86214

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53382

Middle Eastern (MID) AF: 0.00399 AC: 23 AN: 5766

European-Non Finnish (NFE) AF: 0.000317 AC: 352 AN: 1110798

Other (OTH) AF: 0.000547 AC: 33 AN: 60344

GnomAD4 genome AF: 0.000368 AC: 56 AN: 152314 Hom.: 1 Cov.: 32 AF XY: 0.000376 AC XY: 28 AN XY: 74476

African (AFR) AF: 0.0000481 AC: 2 AN: 41564

American (AMR) AF: 0.000523 AC: 8 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68036

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000472 Hom.: 0

Bravo AF: 0.000280

EpiCase AF: 0.000436

EpiControl AF: 0.000948

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HK2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		-0.044
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs138918973; hg19: chr2-75100408;