rs761006775

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001146154.2(PTGR2):​c.616A>C​(p.Ile206Leu) 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 1,461,818 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. I206V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PTGR2
NM_001146154.2 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.824

Publications

1 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3152275).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTGR2NM_001146154.2 linkc.616A>C p.Ile206Leu missense_variant Exon 6 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.616A>C p.Ile206Leu missense_variant Exon 6 of 10 1 NM_001146154.2 ENSP00000452280.1 Q8N8N7-1
ENSG00000258653ENST00000556551.2 linkn.520-863A>C intron_variant Intron 5 of 21 2 ENSP00000451484.1 G3V3Y1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251366
AF XY:
0.00000736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461818
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727210
show subpopulations
⚠️ 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:
33478
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26130
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39688
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53414
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111970
Other (OTH)
AF:
0.00
AC:
0
AN:
60392
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
15
DANN
Benign
0.97
DEOGEN2
Benign
0.057
T;T;T;.
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.34
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.92
.;.;D;D
M_CAP
Benign
0.0064
T
MetaRNN
Benign
0.32
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;M;M;.
PhyloP100
0.82
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-1.7
N;N;N;N
REVEL
Benign
0.17
Sift
Uncertain
0.020
D;D;D;D
Sift4G
Uncertain
0.012
D;D;D;D
Polyphen
0.016
B;B;B;.
Vest4
0.39
MutPred
0.62
Gain of disorder (P = 0.122);Gain of disorder (P = 0.122);Gain of disorder (P = 0.122);.;
MVP
0.014
MPC
0.29
ClinPred
0.35
T
GERP RS
-2.0
Varity_R
0.45
gMVP
0.65
Mutation Taster
=82/18
polymorphism

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

Other links and lift over

dbSNP: rs761006775; hg19: chr14-74345895; API