NM_001146154.2:c.103A>C

Variant names:

• chr14-73860604-A-C
• NM_001146154.2:c.103A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001146154.2(PTGR2):​c.103A>C​(p.Asn35His) 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. 16/22 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: 1.44
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.069096446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGR2	NM_001146154.2	c.103A>C	p.Asn35His	missense_variant	Exon 3 of 10	ENST00000555661.6	NP_001139626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGR2	ENST00000555661.6	c.103A>C	p.Asn35His	missense_variant	Exon 3 of 10	1	NM_001146154.2	ENSP00000452280.1
ENSG00000258653	ENST00000556551.2	n.103A>C		non_coding_transcript_exon_variant	Exon 3 of 22	2		ENSP00000451484.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.103A>C (p.N35H) alteration is located in exon 3 (coding exon 2) of the PTGR2 gene. This alteration results from a A to C substitution at nucleotide position 103, causing the asparagine (N) at amino acid position 35 to be replaced by a histidine (H). 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	0.063
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.022	T;T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.66	.;.;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.069	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L;L
PhyloP100		1.4
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.10	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.26
MutPred		0.40		Loss of catalytic residue at N35 (P = 0.0932);Loss of catalytic residue at N35 (P = 0.0932);Loss of catalytic residue at N35 (P = 0.0932);
MVP		0.030
MPC		0.17
ClinPred		0.28	T
GERP RS		4.7
PromoterAI		0.063	Neutral
Varity_R		0.13
gMVP		0.28
Mutation Taster		=90/10	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

Other links and lift over

hg19: chr14-74327307;