12-132619443-G-T

Position:

• chr12-132619443-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_170682.4(P2RX2):​c.178G>T​(p.Val60Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: P2RX2 NM_170682.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.84

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.761
• PP5: Variant 12-132619443-G-T is Pathogenic according to our data. Variant chr12-132619443-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 155762.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-132619443-G-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX2	NM_170682.4	c.178G>T	p.Val60Leu	missense_variant	2/11	ENST00000643471.2	NP_733782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX2	ENST00000643471.2	c.178G>T	p.Val60Leu	missense_variant	2/11		NM_170682.4	ENSP00000494644	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 41 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 05, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.40	T
M_CAP	Pathogenic	0.93	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PROVEAN	Benign	0.14	N
REVEL	Benign	0.23
Sift	Benign	0.15	T
Sift4G	Benign	0.066	T
Polyphen		0.63	P
Vest4		0.51
MutPred		0.71		Loss of MoRF binding (P = 0.0155);
MVP		0.60
ClinPred		0.99	D
GERP RS		4.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: 15

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs587777692; hg19: chr12-133196029;