rs116834114

Variant names:

• chr12-132621888-T-A
• rs116834114
• NM_170682.4:c.1332T>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_170682.4(P2RX2):​c.1332T>A​(p.Pro444Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000518 in 1,608,504 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00029 (3 hom.)
• Consequence: P2RX2 NM_170682.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.24
• Publications: 0 publications found

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]

P2RX2 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 41

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000280311 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 12-132621888-T-A is Benign according to our data. Variant chr12-132621888-T-A is described in ClinVar as Benign. ClinVar VariationId is 226981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.
• BS2: High AC in GnomAd4 at 407 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170682.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX2	NM_170682.4	MANE Select	c.1332T>A	p.Pro444Pro	synonymous	Exon 11 of 11	NP_733782.1	Q9UBL9-1
	P2RX2	NM_170683.4		c.1410T>A	p.Pro470Pro	synonymous	Exon 10 of 10	NP_733783.1	Q9UBL9-4
	P2RX2	NM_016318.4		c.1260T>A	p.Pro420Pro	synonymous	Exon 10 of 10	NP_057402.1	Q9UBL9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX2	ENST00000643471.2	MANE Select	c.1332T>A	p.Pro444Pro	synonymous	Exon 11 of 11	ENSP00000494644.1	Q9UBL9-1
	P2RX2	ENST00000343948.8	TSL:1	c.1410T>A	p.Pro470Pro	synonymous	Exon 10 of 10	ENSP00000343339.4	Q9UBL9-4
	P2RX2	ENST00000350048.9	TSL:1	c.1260T>A	p.Pro420Pro	synonymous	Exon 10 of 10	ENSP00000343904.5	Q9UBL9-3

Frequencies

GnomAD3 genomes AF: 0.00272 AC: 407 AN: 149502 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000592

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: 0.00242

GnomAD2 exomes AF: 0.000735 AC: 184 AN: 250390 AF XY: 0.000546

Gnomad AFR exome AF: 0.0104

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000292 AC: 426 AN: 1458884 Hom.: 3 Cov.: 34 AF XY: 0.000233 AC XY: 169 AN XY: 725944

African (AFR) AF: 0.0114 AC: 358 AN: 31482

American (AMR) AF: 0.000561 AC: 25 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111924

Other (OTH) AF: 0.000648 AC: 39 AN: 60182

GnomAD4 genome AF: 0.00272 AC: 407 AN: 149620 Hom.: 2 Cov.: 33 AF XY: 0.00269 AC XY: 197 AN XY: 73180

African (AFR) AF: 0.0100 AC: 392 AN: 39014

American (AMR) AF: 0.000591 AC: 9 AN: 15216

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68004

Other (OTH) AF: 0.00239 AC: 5 AN: 2090

Alfa AF: 0.000960 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.10
DANN	Benign	0.74
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs116834114; hg19: chr12-133198474;