12-132618993-CGCGGGGCGCGGGGT-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_170682.4(P2RX2):c.173+28_173+41del variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 1,150,744 control chromosomes in the GnomAD database, including 225,815 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (30049 hom., cov: 0)
  • Exomes 𝑓: 0.61 (195766 hom.)
• Consequence: P2RX2 NM_170682.4 splice_donor_5th_base, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.00

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 Benign. Variant got -16 ACMG points.

• BP6: Variant 12-132618993-CGCGGGGCGCGGGGT-C is Benign according to our data. Variant chr12-132618993-CGCGGGGCGCGGGGT-C is described in ClinVar as [Benign]. Clinvar id is 508104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX2	NM_170682.4	c.173+28_173+41del		splice_donor_5th_base_variant, intron_variant		ENST00000643471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX2	ENST00000643471.2	c.173+28_173+41del		splice_donor_5th_base_variant, intron_variant			NM_170682.4	A2

Frequencies

GnomAD3 genomes AF: 0.678 AC: 84084 AN: 124046 Hom.: 30002 Cov.: 0

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.660

GnomAD3 exomes AF: 0.643 AC: 52932 AN: 82320 Hom.: 18709 AF XY: 0.629 AC XY: 29029 AN XY: 46154

Gnomad AFR exome AF: 0.878

Gnomad AMR exome AF: 0.836

Gnomad ASJ exome AF: 0.499

Gnomad EAS exome AF: 0.829

Gnomad SAS exome AF: 0.619

Gnomad FIN exome AF: 0.549

Gnomad NFE exome AF: 0.584

Gnomad OTH exome AF: 0.623

GnomAD4 exome AF: 0.609 AC: 624741 AN: 1026620 Hom.: 195766 AF XY: 0.609 AC XY: 298151 AN XY: 489498

Gnomad4 AFR exome AF: 0.868

Gnomad4 AMR exome AF: 0.821

Gnomad4 ASJ exome AF: 0.556

Gnomad4 EAS exome AF: 0.839

Gnomad4 SAS exome AF: 0.594

Gnomad4 FIN exome AF: 0.599

Gnomad4 NFE exome AF: 0.593

Gnomad4 OTH exome AF: 0.629

GnomAD4 genome AF: 0.678 AC: 84172 AN: 124124 Hom.: 30049 Cov.: 0 AF XY: 0.680 AC XY: 40363 AN XY: 59342

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.663

Alfa AF: 0.462 Hom.: 1007

Asia WGS AF: 0.658 AC: 2102 AN: 3200

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 12, 2018	- -

Autosomal dominant nonsyndromic hearing loss 41 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200710959; hg19: chr12-133195579;