chr14-73858881-G-A

Variant names:

• chr14-73858881-G-A
• rs771756200
• NM_001146154.2:c.19G>A

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.19G>A​(p.Val7Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,611,612 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: PTGR2 NM_001146154.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.17
• 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=0.10171679).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGR2	NM_001146154.2	c.19G>A	p.Val7Ile	missense_variant	Exon 2 of 10	ENST00000555661.6	NP_001139626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGR2	ENST00000555661.6	c.19G>A	p.Val7Ile	missense_variant	Exon 2 of 10	1	NM_001146154.2	ENSP00000452280.1
ENSG00000258653	ENST00000556551.2	n.19G>A		non_coding_transcript_exon_variant	Exon 2 of 22	2		ENSP00000451484.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152066 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1459546 Hom.: 0 Cov.: 29 AF XY: 0.0000179 AC XY: 13 AN XY: 726170

African (AFR) AF: 0.000209 AC: 7 AN: 33416

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26048

East Asian (EAS) AF: 0.00 AC: 0 AN: 39586

South Asian (SAS) AF: 0.00 AC: 0 AN: 86038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53284

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5756

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1110500

Other (OTH) AF: 0.0000664 AC: 4 AN: 60226

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152066 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74304

African (AFR) AF: 0.00 AC: 0 AN: 41370

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.19G>A (p.V7I) alteration is located in exon 2 (coding exon 1) of the PTGR2 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the valine (V) at amino acid position 7 to be replaced by an isoleucine (I). 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	0.093
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.026	T;T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.0059
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.73	.;.;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L;L
PhyloP100		3.2
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.29	N;N;N
REVEL	Benign	0.062
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.17
MutPred		0.44		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.030
MPC		0.14
ClinPred		0.18	T
GERP RS		3.9
Varity_R		0.064
gMVP		0.26
Mutation Taster		=87/13	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

dbSNP: rs771756200; hg19: chr14-74325584;