12-132620010-T-C

Variant names:

• chr12-132620010-T-C
• rs7964634
• NM_170682.4:c.468T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_170682.4(P2RX2):​c.468T>C​(p.Thr156Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,581,932 control chromosomes in the GnomAD database, including 299,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (35087 hom., cov: 33)
  • Exomes 𝑓: 0.61 (264714 hom.)
• Consequence: P2RX2 NM_170682.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -9.34
• Publications: 20 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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.002).
• BP6: Variant 12-132620010-T-C is Benign according to our data. Variant chr12-132620010-T-C is described in ClinVar as Benign. ClinVar VariationId is 226984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-9.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

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.468T>C	p.Thr156Thr	synonymous	Exon 5 of 11	NP_733782.1	Q9UBL9-1
	P2RX2	NM_170683.4		c.468T>C	p.Thr156Thr	synonymous	Exon 5 of 10	NP_733783.1	Q9UBL9-4
	P2RX2	NM_016318.4		c.396T>C	p.Thr132Thr	synonymous	Exon 4 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.468T>C	p.Thr156Thr	synonymous	Exon 5 of 11	ENSP00000494644.1	Q9UBL9-1
	P2RX2	ENST00000343948.8	TSL:1	c.468T>C	p.Thr156Thr	synonymous	Exon 5 of 10	ENSP00000343339.4	Q9UBL9-4
	P2RX2	ENST00000350048.9	TSL:1	c.396T>C	p.Thr132Thr	synonymous	Exon 4 of 10	ENSP00000343904.5	Q9UBL9-3

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101874 AN: 152028 Hom.: 35048 Cov.: 33

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.641

GnomAD2 exomes AF: 0.637 AC: 126913 AN: 199238 AF XY: 0.624

Gnomad AFR exome AF: 0.805

Gnomad AMR exome AF: 0.790

Gnomad ASJ exome AF: 0.510

Gnomad EAS exome AF: 0.806

Gnomad FIN exome AF: 0.550

Gnomad NFE exome AF: 0.576

Gnomad OTH exome AF: 0.621

GnomAD4 exome AF: 0.605 AC: 865670 AN: 1429786 Hom.: 264714 Cov.: 43 AF XY: 0.604 AC XY: 427853 AN XY: 708406

African (AFR) AF: 0.810 AC: 26766 AN: 33028

American (AMR) AF: 0.780 AC: 31130 AN: 39888

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 12956 AN: 25540

East Asian (EAS) AF: 0.807 AC: 30881 AN: 38284

South Asian (SAS) AF: 0.596 AC: 48698 AN: 81648

European-Finnish (FIN) AF: 0.555 AC: 27586 AN: 49726

Middle Eastern (MID) AF: 0.594 AC: 2974 AN: 5004

European-Non Finnish (NFE) AF: 0.591 AC: 648503 AN: 1097514

Other (OTH) AF: 0.612 AC: 36176 AN: 59154

GnomAD4 genome AF: 0.670 AC: 101968 AN: 152146 Hom.: 35087 Cov.: 33 AF XY: 0.670 AC XY: 49808 AN XY: 74388

African (AFR) AF: 0.811 AC: 33682 AN: 41526

American (AMR) AF: 0.735 AC: 11242 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1757 AN: 3472

East Asian (EAS) AF: 0.805 AC: 4155 AN: 5164

South Asian (SAS) AF: 0.609 AC: 2940 AN: 4824

European-Finnish (FIN) AF: 0.560 AC: 5928 AN: 10594

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40201 AN: 67958

Other (OTH) AF: 0.644 AC: 1361 AN: 2114

Alfa AF: 0.616 Hom.: 17992

Bravo AF: 0.689

Asia WGS AF: 0.696 AC: 2419 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	Autosomal dominant nonsyndromic hearing loss 41 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.13
DANN	Benign	0.58
PhyloP100		-9.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7964634; hg19: chr12-133196596; COSMIC: COSV57675449; COSMIC: COSV57675449;