Genetic Variant PFKFB2:c.*283T>A (chr1-207079302-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000367079.3(PFKFB2):c.*283T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 518,216 control chromosomes in the GnomAD database, including 4,286 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 0.11 ( 1089 hom., cov: 32)

Exomes 𝑓: 0.13 ( 3197 hom. )

Consequence

PFKFB2
ENST00000367079.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0550

Publications

15 publications found

Variant links:

Genes affected

PFKFB2 (HGNC:8873): (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2) The protein encoded by this gene is involved in both the synthesis and degradation of fructose-2,6-bisphosphate, a regulatory molecule that controls glycolysis in eukaryotes. The encoded protein has a 6-phosphofructo-2-kinase activity that catalyzes the synthesis of fructose-2,6-bisphosphate, and a fructose-2,6-biphosphatase activity that catalyzes the degradation of fructose-2,6-bisphosphate. This protein regulates fructose-2,6-bisphosphate levels in the heart, while a related enzyme encoded by a different gene regulates fructose-2,6-bisphosphate levels in the liver and muscle. This enzyme functions as a homodimer. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PFKFB2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
PFKFB2	NM_001018053.2 link	c.*283T>A	3_prime_UTR_variant	Exon 15 of 15	NP_001018063.1	O60825-2
PFKFB2	XM_024447657.2 link	c.*283T>A	3_prime_UTR_variant	Exon 15 of 15	XP_024303425.1
PFKFB2	XM_047422549.1 link	c.*283T>A	3_prime_UTR_variant	Exon 15 of 15	XP_047278505.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
PFKFB2	ENST00000367079.3 link	c.*283T>A	3_prime_UTR_variant	Exon 15 of 15	1	ENSP00000356046.2	O60825-2
PFKFB2	ENST00000473310.5 link	n.519T>A	non_coding_transcript_exon_variant	Exon 3 of 3	2
PFKFB2	ENST00000411990.6 link	n.*1481T>A	downstream_gene_variant		2	ENSP00000408717.3	F6XNB3

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17336

AN:

152132

Hom.:

1087

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0591

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.0899

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.140

GnomAD4 exome

AF:

0.129

AC:

47386

AN:

365966

Hom.:

3197

Cov.:

AF XY:

0.129

AC XY:

24772

AN XY:

192598

show subpopulations

African (AFR)

AF:

0.0572

AC:

609

AN:

10642

American (AMR)

AF:

0.146

AC:

2169

AN:

14900

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

1435

AN:

11278

East Asian (EAS)

AF:

0.117

AC:

2830

AN:

24156

South Asian (SAS)

AF:

0.109

AC:

4424

AN:

40404

European-Finnish (FIN)

AF:

0.136

AC:

3103

AN:

22876

Middle Eastern (MID)

AF:

0.160

AC:

259

AN:

1614

European-Non Finnish (NFE)

AF:

0.137

AC:

29872

AN:

218732

Other (OTH)

AF:

0.126

AC:

2685

AN:

21364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1896

3792

5688

7584

9480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

352

528

704

880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.114

AC:

17338

AN:

152250

Hom.:

1089

Cov.:

AF XY:

0.115

AC XY:

8550

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0590

AC:

2452

AN:

41560

American (AMR)

AF:

0.158

AC:

2415

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

407

AN:

3470

East Asian (EAS)

AF:

0.0902

AC:

467

AN:

5180

South Asian (SAS)

AF:

0.110

AC:

530

AN:

4824

European-Finnish (FIN)

AF:

0.131

AC:

1390

AN:

10598

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9204

AN:

67996

Other (OTH)

AF:

0.138

AC:

293

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

763

1526

2288

3051

3814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0640

Hom.:

Bravo

AF:

0.112

Asia WGS

AF:

0.0960

AC:

335

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.5

(source)

DANN

Benign

0.86

PhyloP100

0.055

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over