Genetic Variant NM_002562.6:c.1745C>G (chr12-121184759-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_002562.6(P2RX7):c.1745C>G(p.Pro582Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000714 in 1,401,190 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: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

P2RX7
NM_002562.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.62

Publications

0 publications found

Variant links:

Genes affected

P2RX7 (HGNC:8537): (purinergic receptor P2X 7) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel and is responsible for ATP-dependent lysis of macrophages through the formation of membrane pores permeable to large molecules. Activation of this nuclear receptor by ATP in the cytoplasm may be a mechanism by which cellular activity can be coupled to changes in gene expression. Multiple alternatively spliced variants have been identified, most of which fit nonsense-mediated decay (NMD) criteria. [provided by RefSeq, Jul 2010]

P2RX7 links:

ENSG00000286248 (HGNC:):

ENSG00000286248 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.757

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002562.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
P2RX7	NM_002562.6	MANE Select	c.1745C>G	p.Pro582Arg	missense	Exon 13 of 13	NP_002553.3
P2RX7	NR_033948.2		n.2063C>G		non_coding_transcript_exon	Exon 13 of 13
P2RX7	NR_033949.2		n.1979C>G		non_coding_transcript_exon	Exon 14 of 14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.1745C>G	p.Pro582Arg	missense	Exon 13 of 13	ENSP00000330696.6
P2RX7	ENST00000261826.10	TSL:1	n.*1198C>G		non_coding_transcript_exon	Exon 12 of 12	ENSP00000261826.6
P2RX7	ENST00000538011.5	TSL:1	n.*1500C>G		non_coding_transcript_exon	Exon 14 of 14	ENSP00000439247.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.14e-7

AC:

AN:

1401190

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

691410

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31680

American (AMR)

AF:

0.00

AC:

AN:

35976

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25306

East Asian (EAS)

AF:

0.00

AC:

AN:

35878

South Asian (SAS)

AF:

0.00

AC:

AN:

79574

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48882

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

9.26e-7

AC:

AN:

1080082

Other (OTH)

AF:

0.00

AC:

AN:

58124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.35

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.62

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.78

M_CAP

Benign

0.024

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.29

MutationAssessor

Uncertain

2.8

PhyloP100

5.6

PrimateAI

Uncertain

0.53

REVEL

Uncertain

0.33

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.88

MutPred

0.37

Gain of MoRF binding (P = 6e-04)

MVP

0.76

ClinPred

0.97

GERP RS

5.5

Varity_R

0.12

gMVP

0.78

Mutation Taster

=46/54

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over