Genetic Variant PTGR2:p.Phe23Leu (chr14-73860570-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001146154.2(PTGR2):c.69C>A(p.Phe23Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F23Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PTGR2
NM_001146154.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.44

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.852

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146154.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTGR2	NM_001146154.2	MANE Select	c.69C>A	p.Phe23Leu	missense	Exon 3 of 10	NP_001139626.1	Q8N8N7-1
PTGR2	NM_001146155.3		c.69C>A	p.Phe23Leu	missense	Exon 3 of 10	NP_001139627.1	Q8N8N7-1
PTGR2	NM_001371325.1		c.69C>A	p.Phe23Leu	missense	Exon 3 of 10	NP_001358254.1	Q8N8N7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTGR2	ENST00000555661.6	TSL:1 MANE Select	c.69C>A	p.Phe23Leu	missense	Exon 3 of 10	ENSP00000452280.1	Q8N8N7-1
PTGR2	ENST00000267568.8	TSL:1	c.69C>A	p.Phe23Leu	missense	Exon 3 of 10	ENSP00000267568.4	Q8N8N7-1
PTGR2	ENST00000553326.5	TSL:1	n.175C>A		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1425546

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709886

African (AFR)

AF:

0.00

AC:

AN:

32006

American (AMR)

AF:

0.00

AC:

AN:

41006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25582

East Asian (EAS)

AF:

0.00

AC:

AN:

38986

South Asian (SAS)

AF:

0.00

AC:

AN:

81564

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5648

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1088506

Other (OTH)

AF:

0.00

AC:

AN:

59176

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.041

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.3

PhyloP100

3.4

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-4.8

REVEL

Uncertain

0.33

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.85

MutPred

0.69

Gain of disorder (P = 0.1149)

MVP

0.16

MPC

0.74

ClinPred

0.99

GERP RS

4.9

PromoterAI

-0.022

Neutral

(source)

Varity_R

0.92

gMVP

0.82

Mutation Taster

=22/78

disease causing

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over