NM_001146154.2:c.416C>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001146154.2(PTGR2):​c.416C>A​(p.Thr139Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. T139S) 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

7
11
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.80

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]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.983

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTGR2NM_001146154.2 linkc.416C>A p.Thr139Asn 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
PTGR2ENST00000555661.6 linkc.416C>A p.Thr139Asn missense_variant Exon 5 of 10 1 NM_001146154.2 ENSP00000452280.1 Q8N8N7-1
ENSG00000258653ENST00000556551.2 linkn.416C>A non_coding_transcript_exon_variant Exon 5 of 22 2 ENSP00000451484.1 G3V3Y1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461602
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727132
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33476
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86246
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5744
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111770
Other (OTH)
AF:
0.00
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.92
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.43
T;T;T;.
Eigen
Pathogenic
0.99
Eigen_PC
Pathogenic
0.91
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.93
.;.;D;T
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.98
D;D;D;D
MetaSVM
Uncertain
0.63
D
MutationAssessor
Pathogenic
4.6
H;H;H;.
PhyloP100
5.8
PrimateAI
Uncertain
0.53
T
PROVEAN
Pathogenic
-4.7
D;D;D;D
REVEL
Pathogenic
0.66
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;D
Polyphen
1.0
D;D;D;.
Vest4
0.90
MutPred
0.91
Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);.;
MVP
0.56
MPC
0.74
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.93
gMVP
0.95
Mutation Taster
=30/70
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs1854490815; hg19: chr14-74343768; API