Genetic Variant PTGR2:p.Leu126Phe (chr14-73877025-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001146154.2(PTGR2):c.376C>T(p.Leu126Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L126V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PTGR2
NM_001146154.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.90

Publications

0 publications found

Variant links:

Genes affected

PTGR2 (HGNC:20149): (prostaglandin reductase 2) This gene encodes an enzyme involved in the metabolism of prostaglandins. The encoded protein catalyzes the NADPH-dependent conversion of 15-keto-prostaglandin E2 to 15-keto-13,14-dihydro-prostaglandin E2. This protein may also be involved in regulating activation of the peroxisome proliferator-activated receptor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

PTGR2 links:

ENSG00000258653 (HGNC:):

ENSG00000258653 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19503456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGR2	NM_001146154.2 link	c.376C>T	p.Leu126Phe	missense_variant	Exon 5 of 10	ENST00000555661.6	NP_001139626.1	Q8N8N7-1V9HW32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGR2	ENST00000555661.6 link	c.376C>T	p.Leu126Phe	missense_variant	Exon 5 of 10	1	NM_001146154.2	ENSP00000452280.1		Q8N8N7-1
ENSG00000258653	ENST00000556551.2 link	n.376C>T		non_coding_transcript_exon_variant	Exon 5 of 22	2		ENSP00000451484.1		G3V3Y1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1460990

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726836

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33432

American (AMR)

AF:

0.00

AC:

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5480

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111688

Other (OTH)

AF:

0.00

AC:

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.083

T;T;T

Eigen

Benign

0.092

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.81

.;.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Pathogenic

3.7

H;H;H

PhyloP100

1.9

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.19

T;T;T

Sift4G

Benign

0.23

T;T;T

Polyphen

0.014

B;B;B

Vest4

0.36

MutPred

0.54

Gain of catalytic residue at L126 (P = 0.0438);Gain of catalytic residue at L126 (P = 0.0438);Gain of catalytic residue at L126 (P = 0.0438);

MVP

0.32

MPC

0.19

ClinPred

0.98

GERP RS

4.9

Varity_R

0.38

gMVP

0.75

Mutation Taster

=51/49

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

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

Publications

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14-73877025-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over