rs757748091
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_170682.4(P2RX2):c.906-13G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,828 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
P2RX2
NM_170682.4 splice_polypyrimidine_tract, intron
NM_170682.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.143
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BS2
?
High AC in GnomAdExome4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
P2RX2 | NM_170682.4 | c.906-13G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000643471.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
P2RX2 | ENST00000643471.2 | c.906-13G>A | splice_polypyrimidine_tract_variant, intron_variant | NM_170682.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152104Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251200Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135738
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461724Hom.: 0 Cov.: 34 AF XY: 0.00000825 AC XY: 6AN XY: 727156
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152104Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74300
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 02, 2016 | Variant classified as Uncertain Significance - Favor Benign. The c.906-13G>A var iant in P2RX2 has not been previously reported in individuals with hearing loss, but has been identified in 2/8652 of East Asian chromosomes by the Exome Aggreg ation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs757748091). Alth ough this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. This variant is located in the 3' spl ice region. Computational tools do not suggest an impact to splicing. However, t his information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the c.906-13G>A variant is uncertain, these d ata suggest that it is more likely to be benign. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at