ENST00000449132.6:c.592C>T

Variant names:

• chr12-132620508-C-T
• rs113782309
• ENST00000449132.6:c.592C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000449132.6(P2RX2):​c.592C>T​(p.Pro198Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,614,036 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P198L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0055 (8 hom., cov: 34)
  • Exomes 𝑓: 0.00079 (5 hom.)
• Consequence: P2RX2 ENST00000449132.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.396

Genes affected

P2RX2 (HGNC:15459): (purinergic receptor P2X 2) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel. Binding to ATP mediates synaptic transmission between neurons and from neurons to smooth muscle. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036708117).
• BP6: Variant 12-132620508-C-T is Benign according to our data. Variant chr12-132620508-C-T is described in ClinVar as [Benign]. Clinvar id is 226987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-132620508-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00551 (839/152332) while in subpopulation AFR AF= 0.0162 (675/41578). AF 95% confidence interval is 0.0152. There are 8 homozygotes in gnomad4. There are 426 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 839 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX2	NM_170682.4	c.699C>T	p.Asp233Asp	synonymous_variant	Exon 7 of 11	ENST00000643471.2	NP_733782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX2	ENST00000643471.2	c.699C>T	p.Asp233Asp	synonymous_variant	Exon 7 of 11		NM_170682.4	ENSP00000494644.1

Frequencies

GnomAD3 genomes AF: 0.00547 AC: 832 AN: 152214 Hom.: 7 Cov.: 34

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00746

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00180 AC: 452 AN: 251254 Hom.: 5 AF XY: 0.00142 AC XY: 193 AN XY: 135828

Gnomad AFR exome AF: 0.0179

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000413

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000789 AC: 1153 AN: 1461704 Hom.: 5 Cov.: 43 AF XY: 0.000704 AC XY: 512 AN XY: 727164

Gnomad4 AFR exome AF: 0.0164

Gnomad4 AMR exome AF: 0.00302

Gnomad4 ASJ exome AF: 0.000421

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000309

Gnomad4 OTH exome AF: 0.00166

GnomAD4 genome AF: 0.00551 AC: 839 AN: 152332 Hom.: 8 Cov.: 34 AF XY: 0.00572 AC XY: 426 AN XY: 74488

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.00745

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00206 Hom.: 3

Bravo AF: 0.00642

ESP6500AA AF: 0.0170 AC: 75

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.00184 AC: 223

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Asp233Asp in exon 7 of P2RX2: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 1.7% (75/4406) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs113782309). -

Apr 14, 2020

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Sep 28, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.2
DANN	Uncertain	0.99
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.12
Sift	Benign	0.27	T
Sift4G	Benign	0.44	T
Polyphen		0.99	D
Vest4		0.19
MVP		0.20
ClinPred		0.0027	T
GERP RS		1.7

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: rs113782309; hg19: chr12-133197094;