NM_001042702.5(PJVK):c.499C>T (p.Arg167Ter) AND Rare genetic deafness

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 1, 2020
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:: RCV000223480.5

Allele description [Variation Report for NM_001042702.5(PJVK):c.499C>T (p.Arg167Ter)]

NM_001042702.5(PJVK):c.499C>T (p.Arg167Ter)

Gene:

PJVK:pejvakin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001042702.5(PJVK):c.499C>T (p.Arg167Ter)

HGVS:

NC_000002.12:g.178456101C>T
NG_009053.1:g.131G>A
NG_012186.1:g.9666C>T
NM_001042702.5:c.499C>TMANE SELECT
NM_001353775.2:c.508C>T
NM_001353776.2:c.604C>T
NM_001353777.1:c.22C>T
NM_001353778.2:c.22C>T
NM_001369912.1:c.499C>T
NP_001036167.1:p.Arg167Ter
NP_001340704.1:p.Arg170Ter
NP_001340705.1:p.Arg202Ter
NP_001340706.1:p.Arg8Ter
NP_001340707.1:p.Arg8Ter
NP_001356841.1:p.Arg167Ter
NC_000002.11:g.179320828C>T
NM_001042702.3:c.499C>T
p.Arg167X

Protein change:

R167*; ARG167TER

Links:

OMIM: 610219.0004; dbSNP: rs118203989

NCBI 1000 Genomes Browser:

rs118203989

Molecular consequence:

NM_001042702.5:c.499C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001353775.2:c.508C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001353776.2:c.604C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001353777.1:c.22C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001353778.2:c.22C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369912.1:c.499C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Rare genetic deafness
Identifiers:: MedGen: C5680250; Orphanet: 96210

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000271351	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 1, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17373699, 23804846, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000271351

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 1, 2020)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Involvement of DFNB59 mutations in autosomal recessive nonsyndromic hearing impairment.

Collin RW, Kalay E, Oostrik J, Caylan R, Wollnik B, Arslan S, den Hollander AI, Birinci Y, Lichtner P, Strom TM, Toraman B, Hoefsloot LH, Cremers CW, Brunner HG, Cremers FP, Karaguzel A, Kremer H.

Hum Mutat. 2007 Jul;28(7):718-23.

PubMed [citation]

PMID:: 17373699

Advancing genetic testing for deafness with genomic technology.

Shearer AE, Black-Ziegelbein EA, Hildebrand MS, Eppsteiner RW, Ravi H, Joshi S, Guiffre AC, Sloan CM, Happe S, Howard SD, Novak B, Deluca AP, Taylor KR, Scheetz TE, Braun TA, Casavant TL, Kimberling WJ, Leproust EM, Smith RJ.

J Med Genet. 2013 Sep;50(9):627-34. doi: 10.1136/jmedgenet-2013-101749. Epub 2013 Jun 26.

PubMed [citation]

PMID:: 23804846
PMCID:: PMC3887546

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000271351.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.Arg167X variant in DFNB59 has been reported in 2 individuals with hearing loss (1 Turkish and 1 Iranian), and segregated with disease in at least 1 affected family member (Collin 2007, Akhtarkhavari 2014). All affected individuals were homozygous. This variant has been identified in 0.01% (18/128640) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This nonsense variant leads to a premature termination codon at position 167, which is predicted to lead to a truncated or absent protein. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive hearing loss. ACMG/AMP Criteria applied: PVS1, PM2_Supporting, PM3, PP1_Supporting.

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

Last Updated: Oct 8, 2024

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