chr12-132618872-G-C

Variant names:

• chr12-132618872-G-C
• NM_170682.4:c.56G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_170682.4(P2RX2):​c.56G>C​(p.Arg19Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000817 in 1,224,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: P2RX2 NM_170682.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.713

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15244767).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX2	NM_170682.4	c.56G>C	p.Arg19Pro	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.56G>C	p.Arg19Pro	missense_variant	Exon 1 of 11		NM_170682.4	ENSP00000494644.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 8.17e-7 AC: 1 AN: 1224210 Hom.: 0 Cov.: 31 AF XY: 0.00000166 AC XY: 1 AN XY: 601514

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: 0.0000210

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.17	T;T;.;.;.;.;.;.;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.69	.;T;T;T;T;T;T;T;T
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.15	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	L;L;L;L;L;L;L;L;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.0	.;N;N;N;N;N;N;N;.
REVEL	Benign	0.11
Sift	Benign	0.082	.;T;D;T;T;T;D;T;.
Sift4G	Benign	0.14	.;T;T;T;D;T;T;T;T
Polyphen		0.0040	B;B;B;B;P;B;P;B;B
Vest4		0.55, 0.47, 0.53, 0.49, 0.53, 0.57, 0.55, 0.56
MutPred		0.59		Loss of MoRF binding (P = 4e-04);Loss of MoRF binding (P = 4e-04);Loss of MoRF binding (P = 4e-04);Loss of MoRF binding (P = 4e-04);Loss of MoRF binding (P = 4e-04);Loss of MoRF binding (P = 4e-04);Loss of MoRF binding (P = 4e-04);Loss of MoRF binding (P = 4e-04);Loss of MoRF binding (P = 4e-04);
MVP		0.39
MPC		1.2
ClinPred		0.15	T
GERP RS		0.56
Varity_R		0.55
gMVP		0.39

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-133195458;