chr12-132618781-T-C

Variant names:

• chr12-132618781-T-C
• rs7314492
• NM_170682.4:c.-36T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_170682.4(P2RX2):​c.-36T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,196,890 control chromosomes in the GnomAD database, including 9,071 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (837 hom., cov: 29)
  • Exomes 𝑓: 0.12 (8234 hom.)
• Consequence: P2RX2 NM_170682.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.465

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 (BayesDel_noAF=-0.87).
• BP6: Variant 12-132618781-T-C is Benign according to our data. Variant chr12-132618781-T-C is described in ClinVar as [Benign]. Clinvar id is 508567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX2	NM_170682.4	c.-36T>C		5_prime_UTR_variant	Exon 1 of 11	ENST00000643471.2	NP_733782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX2	ENST00000643471	c.-36T>C		5_prime_UTR_variant	Exon 1 of 11		NM_170682.4	ENSP00000494644.1

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13540 AN: 149772 Hom.: 837 Cov.: 29

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.0598

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.0936

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0742

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.0797

GnomAD3 exomes AF: 0.108 AC: 697 AN: 6430 Hom.: 45 AF XY: 0.110 AC XY: 359 AN XY: 3262

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0500

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.167

Gnomad SAS exome AF: 0.0690

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.103

Gnomad OTH exome AF: 0.161

GnomAD4 exome AF: 0.122 AC: 127316 AN: 1047008 Hom.: 8234 Cov.: 28 AF XY: 0.121 AC XY: 60099 AN XY: 496372

Gnomad4 AFR exome AF: 0.0153

Gnomad4 AMR exome AF: 0.0501

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.0836

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.0903 AC: 13536 AN: 149882 Hom.: 837 Cov.: 29 AF XY: 0.0903 AC XY: 6607 AN XY: 73184

Gnomad4 AFR AF: 0.0203

Gnomad4 AMR AF: 0.0598

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.0938

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.0808

Alfa AF: 0.108 Hom.: 120

Bravo AF: 0.0842

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

May 09, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.5
DANN	Benign	0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7314492; hg19: chr12-133195367;