12-132618781-T-C

Variant names:

• chr12-132618781-T-C
• rs7314492
• NM_170682.4:c.-36T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_170682.4(P2RX2):​c.-36T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,196,890 control chromosomes in the GnomAD database, including 9,071 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (837 hom., cov: 29)
  • Exomes 𝑓: 0.12 (8234 hom.)
• Consequence: P2RX2 NM_170682.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.465
• Publications: 6 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-132618781-T-C is Benign according to our data. Variant chr12-132618781-T-C is described in ClinVar as Benign. ClinVar VariationId is 508567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX2	NM_170682.4	MANE Select	c.-36T>C		5_prime_UTR	Exon 1 of 11	NP_733782.1	Q9UBL9-1
	P2RX2	NM_170683.4		c.-36T>C		5_prime_UTR	Exon 1 of 10	NP_733783.1	Q9UBL9-4
	P2RX2	NM_016318.4		c.-36T>C		5_prime_UTR	Exon 1 of 10	NP_057402.1	Q9UBL9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX2	ENST00000643471.2	MANE Select	c.-36T>C		5_prime_UTR	Exon 1 of 11	ENSP00000494644.1	Q9UBL9-1
	P2RX2	ENST00000343948.8	TSL:1	c.-36T>C		upstream_gene	N/A	ENSP00000343339.4	Q9UBL9-4
	P2RX2	ENST00000350048.9	TSL:1	c.-36T>C		upstream_gene	N/A	ENSP00000343904.5	Q9UBL9-3

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13540 AN: 149772 Hom.: 837 Cov.: 29

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.0598

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.0936

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0742

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.0797

GnomAD2 exomes AF: 0.108 AC: 697 AN: 6430 AF XY: 0.110

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0500

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.167

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.103

Gnomad OTH exome AF: 0.161

GnomAD4 exome AF: 0.122 AC: 127316 AN: 1047008 Hom.: 8234 Cov.: 28 AF XY: 0.121 AC XY: 60099 AN XY: 496372

African (AFR) AF: 0.0153 AC: 325 AN: 21250

American (AMR) AF: 0.0501 AC: 349 AN: 6970

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 1581 AN: 12008

East Asian (EAS) AF: 0.220 AC: 4962 AN: 22528

South Asian (SAS) AF: 0.0836 AC: 1764 AN: 21090

European-Finnish (FIN) AF: 0.120 AC: 3242 AN: 27126

Middle Eastern (MID) AF: 0.0659 AC: 191 AN: 2900

European-Non Finnish (NFE) AF: 0.123 AC: 110214 AN: 892880

Other (OTH) AF: 0.116 AC: 4688 AN: 40256

GnomAD4 genome AF: 0.0903 AC: 13536 AN: 149882 Hom.: 837 Cov.: 29 AF XY: 0.0903 AC XY: 6607 AN XY: 73184

African (AFR) AF: 0.0203 AC: 837 AN: 41168

American (AMR) AF: 0.0598 AC: 903 AN: 15110

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 436 AN: 3442

East Asian (EAS) AF: 0.211 AC: 1047 AN: 4964

South Asian (SAS) AF: 0.0938 AC: 451 AN: 4806

European-Finnish (FIN) AF: 0.117 AC: 1148 AN: 9818

Middle Eastern (MID) AF: 0.0759 AC: 22 AN: 290

European-Non Finnish (NFE) AF: 0.124 AC: 8333 AN: 67284

Other (OTH) AF: 0.0808 AC: 169 AN: 2092

Alfa AF: 0.108 Hom.: 120

Bravo AF: 0.0842

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.5
DANN	Benign	0.30
PhyloP100		-0.47
PromoterAI		-0.011	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7314492; hg19: chr12-133195367;