NM_170682.4(P2RX2):c.381+2T>C AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 4, 2016
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000602869.4

Allele description [Variation Report for NM_170682.4(P2RX2):c.381+2T>C]

NM_170682.4(P2RX2):c.381+2T>C

Gene:

P2RX2:purinergic receptor P2X 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.33

Genomic location:

Preferred name:

NM_170682.4(P2RX2):c.381+2T>C

HGVS:

NC_000012.12:g.132619752T>C
NG_033909.1:g.5973T>C
NM_001282164.2:c.310-92T>C
NM_001282165.2:c.381+2T>C
NM_012226.5:c.241+178T>C
NM_016318.4:c.310-92T>C
NM_170682.4:c.381+2T>CMANE SELECT
NM_170683.4:c.381+2T>C
NM_174872.3:c.106-92T>C
NM_174873.3:c.381+2T>C
NC_000012.11:g.133196338T>C
NM_174873.1:c.381+2T>C

Links:

dbSNP: rs200978001

NCBI 1000 Genomes Browser:

rs200978001

Molecular consequence:

NM_001282164.2:c.310-92T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_012226.5:c.241+178T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_016318.4:c.310-92T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_174872.3:c.106-92T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001282165.2:c.381+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_170682.4:c.381+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_170683.4:c.381+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_174873.3:c.381+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000711633	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Dec 4, 2016)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23345450, 25788561, 24211385, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000711633

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Dec 4, 2016)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation of the ATP-gated P2X(2) receptor leads to progressive hearing loss and increased susceptibility to noise.

Yan D, Zhu Y, Walsh T, Xie D, Yuan H, Sirmaci A, Fujikawa T, Wong AC, Loh TL, Du L, Grati M, Vlajkovic SM, Blanton S, Ryan AF, Chen ZY, Thorne PR, Kachar B, Tekin M, Zhao HB, Housley GD, King MC, Liu XZ.

Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2228-33. doi: 10.1073/pnas.1222285110. Epub 2013 Jan 23.

PubMed [citation]

PMID:: 23345450
PMCID:: PMC3568371

Hearing loss caused by a P2RX2 mutation identified in a MELAS family with a coexisting mitochondrial 3243AG mutation.

Moteki H, Azaiez H, Booth KT, Hattori M, Sato A, Sato Y, Motobayashi M, Sloan CM, Kolbe DL, Shearer AE, Smith RJ, Usami S.

Ann Otol Rhinol Laryngol. 2015 May;124 Suppl 1:177S-83S. doi: 10.1177/0003489415575045. Epub 2015 Mar 18.

PubMed [citation]

PMID:: 25788561
PMCID:: PMC4441871

See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000711633.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

Description

The c.381+2T>C variant in P2RX2 has not been previously reported in individuals with hearing loss. It has been identified in 32/119906 European chromosomes by t he Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs200978001). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. This variant occurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predi cted to cause altered splicing leading to an abnormal or absent protein. However , to date only 3 missense variants in P2RX2 have been associated with hearing lo ss (Yan 2013, Faletra 2014, Moteki 2015), and it is not clear if loss-of-functio n variant in P2RX2 can result in hearing loss. In summary, the clinical signific ance of the c.381+2T>C variant is uncertain due to lack of data supporting loss- of-function of P2RX2 as a disease mechanism.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		1	not provided	1	not provided

Last Updated: Sep 29, 2024

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