14-73858872-C-G

Variant names:

• chr14-73858872-C-G
• NM_001146154.2:c.10C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001371330.1(PTGR2):​c.-486C>G variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTGR2 NM_001371330.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.75

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19169986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGR2	NM_001146154.2	c.10C>G	p.Gln4Glu	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.10C>G	p.Gln4Glu	missense_variant	Exon 2 of 10	1	NM_001146154.2	ENSP00000452280.1
ENSG00000258653	ENST00000556551.2	n.10C>G		non_coding_transcript_exon_variant	Exon 2 of 22	2		ENSP00000451484.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.10C>G (p.Q4E) alteration is located in exon 2 (coding exon 1) of the PTGR2 gene. This alteration results from a C to G substitution at nucleotide position 10, causing the glutamine (Q) at amino acid position 4 to be replaced by a glutamic acid (E). 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	0.083
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T;T;T
Eigen	Benign	0.091
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	.;.;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L;L;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.68	N;N;N
REVEL	Benign	0.059
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.20	T;T;T
Polyphen		0.14	B;B;B
Vest4		0.29
MutPred		0.51		Gain of disorder (P = 0.0502);Gain of disorder (P = 0.0502);Gain of disorder (P = 0.0502);
MVP		0.030
MPC		0.18
ClinPred		0.57	D
GERP RS		4.8
Varity_R		0.20
gMVP		0.60

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-74325575;