NM_170682.4:c.115C>T

Variant names:

• chr12-132618931-C-T
• rs778028145
• NM_170682.4:c.115C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_170682.4(P2RX2):​c.115C>T​(p.Arg39Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000605 in 1,321,608 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R39R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: P2RX2 NM_170682.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• 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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 7 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.115C>T	p.Arg39Trp	missense	Exon 1 of 11	NP_733782.1	Q9UBL9-1
	P2RX2	NM_170683.4		c.115C>T	p.Arg39Trp	missense	Exon 1 of 10	NP_733783.1	Q9UBL9-4
	P2RX2	NM_016318.4		c.115C>T	p.Arg39Trp	missense	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.115C>T	p.Arg39Trp	missense	Exon 1 of 11	ENSP00000494644.1	Q9UBL9-1
	P2RX2	ENST00000343948.8	TSL:1	c.115C>T	p.Arg39Trp	missense	Exon 1 of 10	ENSP00000343339.4	Q9UBL9-4
	P2RX2	ENST00000350048.9	TSL:1	c.115C>T	p.Arg39Trp	missense	Exon 1 of 10	ENSP00000343904.5	Q9UBL9-3

Frequencies

GnomAD3 genomes AF: 0.00000671 AC: 1 AN: 148972 Hom.: 0 Cov.: 29

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: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000597 AC: 7 AN: 1172636 Hom.: 0 Cov.: 31 AF XY: 0.00000878 AC XY: 5 AN XY: 569508

African (AFR) AF: 0.00 AC: 0 AN: 24332

American (AMR) AF: 0.00 AC: 0 AN: 17252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14356

East Asian (EAS) AF: 0.00 AC: 0 AN: 29688

South Asian (SAS) AF: 0.0000270 AC: 1 AN: 37098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4546

European-Non Finnish (NFE) AF: 0.00000625 AC: 6 AN: 959532

Other (OTH) AF: 0.00 AC: 0 AN: 45670

GnomAD4 genome AF: 0.00000671 AC: 1 AN: 148972 Hom.: 0 Cov.: 29 AF XY: 0.0000138 AC XY: 1 AN XY: 72664

African (AFR) AF: 0.00 AC: 0 AN: 40766

American (AMR) AF: 0.00 AC: 0 AN: 15110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 5038

South Asian (SAS) AF: 0.00 AC: 0 AN: 4756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 66986

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

Alfa AF: 0.000224 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.42	N
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.87	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.096
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.19
Sift	Benign	0.30	T
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.59
MutPred		0.63		Loss of methylation at R40 (P = 0.0888)
MVP		0.53
MPC		1.9
ClinPred		0.82	D
GERP RS		0.73
PromoterAI		0.0017	Neutral
Varity_R		0.072
gMVP		0.50
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs778028145; hg19: chr12-133195517;