NM_001146154.2:c.573G>C

Variant names:

• chr14-73879149-G-C
• rs2054925762
• NM_001146154.2:c.573G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001146154.2(PTGR2):​c.573G>C​(p.Glu191Asp) 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 benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTGR2 NM_001146154.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25
• Publications: 0 publications found

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]

ENSG00000258653 (HGNC:):

ACMG classification

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=0.35613352).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGR2	NM_001146154.2	c.573G>C	p.Glu191Asp	missense_variant	Exon 6 of 10	ENST00000555661.6	NP_001139626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGR2	ENST00000555661.6	c.573G>C	p.Glu191Asp	missense_variant	Exon 6 of 10	1	NM_001146154.2	ENSP00000452280.1
ENSG00000258653	ENST00000556551.2	n.520-906G>C		intron_variant	Intron 5 of 21	2		ENSP00000451484.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.573G>C (p.E191D) alteration is located in exon 6 (coding exon 5) of the PTGR2 gene. This alteration results from a G to C substitution at nucleotide position 573, causing the glutamic acid (E) at amino acid position 191 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T;T;T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.087
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	.;.;D;D
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.36	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.5	L;L;L;.
PhyloP100		2.2
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Benign	0.078
Sift	Benign	0.18	T;T;T;T
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.024	B;B;B;.
Vest4		0.46
MutPred		0.60		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;
MVP		0.35
MPC		0.20
ClinPred		0.55	D
GERP RS		3.7
Varity_R		0.32
gMVP		0.53
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2054925762; hg19: chr14-74345852;