Genetic Variant NM_170682.4:c.42C>T (chr12-132618858-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_170682.4(P2RX2):c.42C>T(p.Ala14Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,370,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00085 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

P2RX2
NM_170682.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.06

Publications

0 publications found

Variant links:

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]

P2RX2 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 41
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
nonsyndromic genetic hearing loss
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

P2RX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.007).

BP6

Variant 12-132618858-C-T is Benign according to our data. Variant chr12-132618858-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 737628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.06 with no splicing effect.

BS2

High AC in GnomAd4 at 128 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170682.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
P2RX2	NM_170682.4	MANE Select	c.42C>T	p.Ala14Ala	synonymous	Exon 1 of 11	NP_733782.1	Q9UBL9-1
P2RX2	NM_170683.4		c.42C>T	p.Ala14Ala	synonymous	Exon 1 of 10	NP_733783.1	Q9UBL9-4
P2RX2	NM_016318.4		c.42C>T	p.Ala14Ala	synonymous	Exon 1 of 10	NP_057402.1	Q9UBL9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
P2RX2	ENST00000643471.2	MANE Select	c.42C>T	p.Ala14Ala	synonymous	Exon 1 of 11	ENSP00000494644.1	Q9UBL9-1
P2RX2	ENST00000343948.8	TSL:1	c.42C>T	p.Ala14Ala	synonymous	Exon 1 of 10	ENSP00000343339.4	Q9UBL9-4
P2RX2	ENST00000350048.9	TSL:1	c.42C>T	p.Ala14Ala	synonymous	Exon 1 of 10	ENSP00000343904.5	Q9UBL9-3

Frequencies

GnomAD3 genomes

AF:

0.000850

AC:

128

AN:

150558

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00301

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.000966

GnomAD2 exomes

AF:

0.000209

AC:

AN:

114666

AF XY:

0.000168

show subpopulations

Gnomad AFR exome

AF:

0.00311

Gnomad AMR exome

AF:

0.0000887

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000828

AC:

101

AN:

1219486

Hom.:

Cov.:

AF XY:

0.0000835

AC XY:

AN XY:

598640

show subpopulations

African (AFR)

AF:

0.00365

AC:

AN:

24960

American (AMR)

AF:

0.000104

AC:

AN:

19168

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16376

East Asian (EAS)

AF:

0.00

AC:

AN:

30278

South Asian (SAS)

AF:

0.00

AC:

AN:

46162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4544

European-Non Finnish (NFE)

AF:

0.00000101

AC:

AN:

987862

Other (OTH)

AF:

0.000147

AC:

AN:

47738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000850

AC:

128

AN:

150666

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

73568

show subpopulations

African (AFR)

AF:

0.00300

AC:

124

AN:

41374

American (AMR)

AF:

0.0000658

AC:

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

5092

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10030

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67402

Other (OTH)

AF:

0.000956

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000783

Hom.:

Bravo

AF:

0.000982

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

P2RX2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

7.3

(source)

DANN

Benign

0.96

PhyloP100

-1.1

PromoterAI

0.0058

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over