rs876657423

chr12-132621877-ATCTCTGCCCCT-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_170682.4(P2RX2):c.1325_1335del(p.Ser442Ter) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,613,480 control chromosomes in the GnomAD database, including 29 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0089 (14 hom., cov: 33)
  • Exomes 𝑓: 0.00085 (15 hom.)
• Consequence: P2RX2 NM_170682.4 frameshift
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.17

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 12-132621877-ATCTCTGCCCCT-A is Benign according to our data. Variant chr12-132621877-ATCTCTGCCCCT-A is described in ClinVar as [Likely_benign]. Clinvar id is 226980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00892 (1358/152250) while in subpopulation AFR AF= 0.0312 (1297/41542). AF 95% confidence interval is 0.0298. There are 14 homozygotes in gnomad4. There are 643 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 1358 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX2	NM_170682.4	c.1325_1335del	p.Ser442Ter	frameshift_variant	11/11	ENST00000643471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX2	ENST00000643471.2	c.1325_1335del	p.Ser442Ter	frameshift_variant	11/11		NM_170682.4	A2

Frequencies

GnomAD3 genomes AF: 0.00893 AC: 1358 AN: 152132 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

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: 0.0000882

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00236 AC: 591 AN: 250266 Hom.: 4 AF XY: 0.00169 AC XY: 229 AN XY: 135442

Gnomad AFR exome AF: 0.0318

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.0000996

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000531

Gnomad OTH exome AF: 0.000982

GnomAD4 exome AF: 0.000847 AC: 1237 AN: 1461230 Hom.: 15 AF XY: 0.000741 AC XY: 539 AN XY: 726950

Gnomad4 AFR exome AF: 0.0304

Gnomad4 AMR exome AF: 0.00190

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000180

Gnomad4 OTH exome AF: 0.00172

GnomAD4 genome AF: 0.00892 AC: 1358 AN: 152250 Hom.: 14 Cov.: 33 AF XY: 0.00863 AC XY: 643 AN XY: 74466

Gnomad4 AFR AF: 0.0312

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00480 Hom.: 0

Bravo AF: 0.00965

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 22, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 12, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 09, 2016

p.Ala469SerfsX21 in exon 11 of P2RX2 : This variant is not expected to have clin ical significance because it has been identified in 3.4% (344/10052) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs150092274). This variant is located in the last exon of the gene that is alternatively spliced in some isoforms, and is likely to escape nonsens e mediated decay. -

Autosomal dominant nonsyndromic hearing loss 41 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 07, 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: rs876657423; hg19: chr12-133198463;