chr12-132618952-C-G

Variant names:

• chr12-132618952-C-G
• NM_170682.4:c.136C>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_170682.4(P2RX2):​c.136C>G​(p.Arg46Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000174 in 1,150,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: P2RX2 NM_170682.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.852

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_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.951

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX2	NM_170682.4	c.136C>G	p.Arg46Gly	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.136C>G	p.Arg46Gly	missense_variant	Exon 1 of 11		NM_170682.4	ENSP00000494644.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000174 AC: 2 AN: 1150886 Hom.: 0 Cov.: 31 AF XY: 0.00000180 AC XY: 1 AN XY: 555486

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: 0.0000303

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000106

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T;T;.;.;.;.;T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.97	.;D;D;D;D;D;D
M_CAP	Pathogenic	0.97	D
MetaRNN	Pathogenic	0.95	D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.3	M;M;M;M;M;M;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-4.2	.;D;D;D;D;D;.
REVEL	Uncertain	0.31
Sift	Uncertain	0.0020	.;D;D;D;D;D;.
Sift4G	Pathogenic	0.0010	.;D;D;D;D;D;D
Polyphen		0.97	D;D;D;D;D;D;P
Vest4		0.74, 0.32, 0.75, 0.77, 0.55, 0.50
MutPred		0.88		Loss of MoRF binding (P = 0.0067);Loss of MoRF binding (P = 0.0067);Loss of MoRF binding (P = 0.0067);Loss of MoRF binding (P = 0.0067);Loss of MoRF binding (P = 0.0067);Loss of MoRF binding (P = 0.0067);Loss of MoRF binding (P = 0.0067);
MVP		0.61
MPC		2.0
ClinPred		0.98	D
GERP RS		3.2
Varity_R		0.70
gMVP		0.79

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-133195538;