NM_001146154.2:c.263C>A

Variant names:

• chr14-73874129-C-A
• rs200904707
• NM_001146154.2:c.263C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001146154.2(PTGR2):​c.263C>A​(p.Thr88Lys) 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. 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. T88R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTGR2 NM_001146154.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.953
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029507458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGR2	NM_001146154.2	c.263C>A	p.Thr88Lys	missense_variant	Exon 4 of 10	ENST00000555661.6	NP_001139626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGR2	ENST00000555661.6	c.263C>A	p.Thr88Lys	missense_variant	Exon 4 of 10	1	NM_001146154.2	ENSP00000452280.1
ENSG00000258653	ENST00000556551.2	n.263C>A		non_coding_transcript_exon_variant	Exon 4 of 22	2		ENSP00000451484.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.23
DANN	Benign	0.87
DEOGEN2	Benign	0.022	T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.088	.;.;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.030	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.30	N;N;N
PhyloP100		-0.95
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.060	N;N;N
REVEL	Benign	0.043
Sift	Benign	0.84	T;T;T
Sift4G	Benign	0.82	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.14
MutPred		0.32		Gain of ubiquitination at T88 (P = 0.023);Gain of ubiquitination at T88 (P = 0.023);Gain of ubiquitination at T88 (P = 0.023);
MVP		0.21
MPC		0.20
ClinPred		0.024	T
GERP RS		-4.5
Varity_R		0.063
gMVP		0.37
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200904707; hg19: chr14-74340832;