12-132618931-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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.

• 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

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX2	NM_170682.4	c.115C>T	p.Arg39Trp	missense_variant	Exon 1 of 11	ENST00000643471.2	NP_733782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX2	ENST00000643471.2	c.115C>T	p.Arg39Trp	missense_variant	Exon 1 of 11		NM_170682.4	ENSP00000494644.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000270

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000625

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000149

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000224 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;.;.;.;.;T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.42	N
LIST_S2	Uncertain	0.91	.;D;D;D;D;D;D
M_CAP	Pathogenic	0.87	D
MetaRNN	Uncertain	0.51	D;D;D;D;D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	L;L;L;L;L;L;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-2.3	.;N;N;D;D;N;D
REVEL	Benign	0.19
Sift	Benign	0.30	.;T;D;T;T;T;D
Sift4G	Benign	0.16	.;T;T;T;T;T;T
Polyphen		1.0	D;D;D;D;D;D;D
Vest4		0.59, 0.33, 0.58, 0.57, 0.34, 0.30
MutPred		0.63		Loss of methylation at R40 (P = 0.0888);Loss of methylation at R40 (P = 0.0888);Loss of methylation at R40 (P = 0.0888);Loss of methylation at R40 (P = 0.0888);Loss of methylation at R40 (P = 0.0888);Loss of methylation at R40 (P = 0.0888);Loss of methylation at R40 (P = 0.0888);
MVP		0.53
MPC		1.9
ClinPred		0.82	D
GERP RS		0.73
Varity_R		0.072
gMVP		0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs778028145; hg19: chr12-133195517;