chr1-207071700-T-A

Variant names:

• chr1-207071700-T-A
• rs11120137
• NM_006212.2:c.1350+127T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006212.2(PFKFB2):​c.1350+127T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000189 in 528,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PFKFB2 NM_006212.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006212.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKFB2	NM_006212.2	MANE Select	c.1350+127T>A		intron	N/A	NP_006203.2
	PFKFB2	NM_001018053.2		c.1350+127T>A		intron	N/A	NP_001018063.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKFB2	ENST00000367080.8	TSL:1 MANE Select	c.1350+127T>A		intron	N/A	ENSP00000356047.3
	PFKFB2	ENST00000367079.3	TSL:1	c.1350+127T>A		intron	N/A	ENSP00000356046.2
	PFKFB2	ENST00000411990.6	TSL:2	n.*1132+127T>A		intron	N/A	ENSP00000408717.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152014 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000189 AC: 1 AN: 528878 Hom.: 0 AF XY: 0.00000357 AC XY: 1 AN XY: 280066

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 13672

American (AMR) AF: 0.00 AC: 0 AN: 21226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15570

East Asian (EAS) AF: 0.00 AC: 0 AN: 31912

South Asian (SAS) AF: 0.00 AC: 0 AN: 50592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3690

European-Non Finnish (NFE) AF: 0.00000313 AC: 1 AN: 319772

Other (OTH) AF: 0.00 AC: 0 AN: 28182

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152014 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74232

African (AFR) AF: 0.00 AC: 0 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2094

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.13
DANN	Benign	0.38
PhyloP100		-1.2

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: rs11120137; hg19: chr1-207245045;