rs2206593

Positions:

• chr1-186673297-A-G
• chr1-186673297-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000367468.10(PTGS2):​c.*1056T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.954 in 152,298 control chromosomes in the GnomAD database, including 69,377 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.95 (69377 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: PTGS2 ENST00000367468.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

Genes affected

PTGS2 (HGNC:9605): (prostaglandin-endoperoxide synthase 2) Prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase, is the key enzyme in prostaglandin biosynthesis, and acts both as a dioxygenase and as a peroxidase. There are two isozymes of PTGS: a constitutive PTGS1 and an inducible PTGS2, which differ in their regulation of expression and tissue distribution. This gene encodes the inducible isozyme. It is regulated by specific stimulatory events, suggesting that it is responsible for the prostanoid biosynthesis involved in inflammation and mitogenesis. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGS2	NM_000963.4	c.*1056T>C		3_prime_UTR_variant	10/10	ENST00000367468.10	NP_000954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGS2	ENST00000367468.10	c.*1056T>C		3_prime_UTR_variant	10/10	1	NM_000963.4	ENSP00000356438	P1
PTGS2	ENST00000490885.6	n.3286T>C		non_coding_transcript_exon_variant	9/9	1
PTGS2	ENST00000680451.1	c.*1056T>C		3_prime_UTR_variant	11/11			ENSP00000506242	P1
PTGS2	ENST00000681605.1	c.*2543T>C		3_prime_UTR_variant, NMD_transcript_variant	10/10			ENSP00000504900

Frequencies

GnomAD3 genomes AF: 0.954 AC: 145218 AN: 152178 Hom.: 69318 Cov.: 33

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.954

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.922

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.944

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.954 AC: 145335 AN: 152296 Hom.: 69377 Cov.: 33 AF XY: 0.952 AC XY: 70868 AN XY: 74452

Gnomad4 AFR AF: 0.990

Gnomad4 AMR AF: 0.955

Gnomad4 ASJ AF: 0.905

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.930

Gnomad4 FIN AF: 0.922

Gnomad4 NFE AF: 0.939

Gnomad4 OTH AF: 0.944

Alfa AF: 0.939 Hom.: 90385

Bravo AF: 0.959

Asia WGS AF: 0.967 AC: 3357 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.21
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs2206593; hg19: chr1-186642429;