NM_170682.4:c.69C>A

Variant names:

• chr12-132618885-C-A
• rs756774341
• NM_170682.4:c.69C>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP7 BS2

The NM_170682.4(P2RX2):​c.69C>A​(p.Ser23Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000349 in 1,377,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S23S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: P2RX2 NM_170682.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96
• Publications: 2 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.02).
• BP7: Synonymous conserved (PhyloP=-2.96 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 44 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.69C>A	p.Ser23Ser	synonymous	Exon 1 of 11	NP_733782.1	Q9UBL9-1
	P2RX2	NM_170683.4		c.69C>A	p.Ser23Ser	synonymous	Exon 1 of 10	NP_733783.1	Q9UBL9-4
	P2RX2	NM_016318.4		c.69C>A	p.Ser23Ser	synonymous	Exon 1 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.69C>A	p.Ser23Ser	synonymous	Exon 1 of 11	ENSP00000494644.1	Q9UBL9-1
	P2RX2	ENST00000343948.8	TSL:1	c.69C>A	p.Ser23Ser	synonymous	Exon 1 of 10	ENSP00000343339.4	Q9UBL9-4
	P2RX2	ENST00000350048.9	TSL:1	c.69C>A	p.Ser23Ser	synonymous	Exon 1 of 10	ENSP00000343904.5	Q9UBL9-3

Frequencies

GnomAD3 genomes AF: 0.0000266 AC: 4 AN: 150224 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000594

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000776 AC: 1 AN: 128788 AF XY: 0.0000137

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000157

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000359 AC: 44 AN: 1226992 Hom.: 0 Cov.: 31 AF XY: 0.0000332 AC XY: 20 AN XY: 602734

African (AFR) AF: 0.00 AC: 0 AN: 25146

American (AMR) AF: 0.00 AC: 0 AN: 20120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16836

East Asian (EAS) AF: 0.00 AC: 0 AN: 30432

South Asian (SAS) AF: 0.00 AC: 0 AN: 47970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4716

European-Non Finnish (NFE) AF: 0.0000444 AC: 44 AN: 990436

Other (OTH) AF: 0.00 AC: 0 AN: 48182

GnomAD4 genome AF: 0.0000266 AC: 4 AN: 150224 Hom.: 0 Cov.: 28 AF XY: 0.0000409 AC XY: 3 AN XY: 73306

African (AFR) AF: 0.00 AC: 0 AN: 41180

American (AMR) AF: 0.00 AC: 0 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.00 AC: 0 AN: 5108

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000594 AC: 4 AN: 67284

Other (OTH) AF: 0.00 AC: 0 AN: 2054

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.7
DANN	Benign	0.93
PhyloP100		-3.0
PromoterAI		0.028	Neutral

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

Other links and lift over

dbSNP: rs756774341; hg19: chr12-133195471; COSMIC: COSV100268681; COSMIC: COSV100268681;