chr12-132618823-G-A

Variant names:

• chr12-132618823-G-A
• NM_170682.4:c.7G>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_170682.4(P2RX2):​c.7G>A​(p.Ala3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000534 in 1,122,770 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.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000053 (0 hom.)
• Consequence: P2RX2 NM_170682.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06965241).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX2	NM_170682.4	c.7G>A	p.Ala3Thr	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.7G>A	p.Ala3Thr	missense_variant	Exon 1 of 11		NM_170682.4	ENSP00000494644.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000534 AC: 6 AN: 1122770 Hom.: 0 Cov.: 31 AF XY: 0.00000556 AC XY: 3 AN XY: 540006

Gnomad4 AFR exome AF: 0.0000427

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000669

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000320

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	0.18
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;.;.;.;.;.;.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.66	.;T;T;T;T;T;T;T;T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.070	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M;M;M;M;M;M;M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.71	.;N;N;N;N;N;N;N;N
REVEL	Benign	0.056
Sift	Uncertain	0.0080	.;D;D;D;D;D;D;D;D
Sift4G	Benign	0.086	.;T;D;T;D;T;D;T;D
Polyphen		0.99	D;D;D;D;B;D;B;D;D
Vest4		0.30, 0.25, 0.30, 0.29, 0.32, 0.30, 0.31, 0.27
MutPred		0.19		Gain of glycosylation at A3 (P = 0.0043);Gain of glycosylation at A3 (P = 0.0043);Gain of glycosylation at A3 (P = 0.0043);Gain of glycosylation at A3 (P = 0.0043);Gain of glycosylation at A3 (P = 0.0043);Gain of glycosylation at A3 (P = 0.0043);Gain of glycosylation at A3 (P = 0.0043);Gain of glycosylation at A3 (P = 0.0043);Gain of glycosylation at A3 (P = 0.0043);
MVP		0.44
MPC		1.2
ClinPred		0.42	T
GERP RS		1.8
Varity_R		0.10
gMVP		0.25

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: chr12-133195409; COSMIC: COSV100266833; COSMIC: COSV100266833;