NM_001042702.5(PJVK):c.406C>T (p.Arg136Ter) AND Autosomal recessive nonsyndromic hearing loss 59

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 1, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001727794.3

Allele description [Variation Report for NM_001042702.5(PJVK):c.406C>T (p.Arg136Ter)]

NM_001042702.5(PJVK):c.406C>T (p.Arg136Ter)

Gene:

PJVK:pejvakin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001042702.5(PJVK):c.406C>T (p.Arg136Ter)

Other names:

NM_001042702.3:c.406C>T, p.(Arg136*)

HGVS:

NC_000002.12:g.178454526C>T
NG_009053.1:g.1706G>A
NG_012186.1:g.8091C>T
NM_001042702.5:c.406C>TMANE SELECT
NM_001353775.2:c.415C>T
NM_001353776.2:c.511C>T
NM_001353777.1:c.-72C>T
NM_001353778.2:c.-72C>T
NM_001369912.1:c.406C>T
NP_001036167.1:p.Arg136Ter
NP_001340704.1:p.Arg139Ter
NP_001340705.1:p.Arg171Ter
NP_001356841.1:p.Arg136Ter
NC_000002.11:g.179319253C>T
NM_001042702.3:c.406C>T

Protein change:

R136*

Links:

dbSNP: rs367688416

NCBI 1000 Genomes Browser:

rs367688416

Molecular consequence:

NM_001353777.1:c.-72C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001353778.2:c.-72C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001042702.5:c.406C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001353775.2:c.415C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001353776.2:c.511C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369912.1:c.406C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 59
Synonyms:: Deafness, autosomal recessive 59
Identifiers:: MONDO: MONDO:0012445; MedGen: C1857744; Orphanet: 90636; OMIM: 610220

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001976368	King Laboratory, University of Washington	criteria provided, single submitter (Abu Rayyan A et al. (Proc Natl Acad Sci U S A 2020))	Pathogenic (Aug 1, 2020)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV004013831	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19888295, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001976368

King Laboratory, University of Washington

criteria provided, single submitter

(Abu Rayyan A et al. (Proc Natl Acad Sci U S A 2020))

Pathogenic
(Aug 1, 2020)

germline

research

PubMed (1)
[See all records that cite this PMID]

SCV004013831

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

unknown

clinical testing

PubMed (2)
[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	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genomic analysis of inherited hearing loss in the Palestinian population.

Abu Rayyan A, Kamal L, Casadei S, Brownstein Z, Zahdeh F, Shahin H, Canavati C, Dweik D, Jaraysa T, Rabie G, Carlson RJ, Gulsuner S, Lee MK, Avraham KB, Walsh T, King MC, Kanaan MN.

Proc Natl Acad Sci U S A. 2020 Aug 18;117(33):20070-20076. doi: 10.1073/pnas.2009628117. Epub 2020 Aug 3.

PubMed [citation]

PMID:: 32747562
PMCID:: PMC7443947

Five novel loci for inherited hearing loss mapped by SNP-based homozygosity profiles in Palestinian families.

Shahin H, Walsh T, Rayyan AA, Lee MK, Higgins J, Dickel D, Lewis K, Thompson J, Baker C, Nord AS, Stray S, Gurwitz D, Avraham KB, King MC, Kanaan M.

Eur J Hum Genet. 2010 Apr;18(4):407-13. doi: 10.1038/ejhg.2009.190. Epub 2009 Nov 4.

PubMed [citation]

PMID:: 19888295
PMCID:: PMC2987250

See all PubMed Citations (3)

Details of each submission

From King Laboratory, University of Washington, SCV001976368.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

Description

PJVK c.406C>T, p.R136* is homozygous in 2 children and their father with profound hearing loss in a Palestinian family (Abu Rayyan 2020). It is absent from 1300 Palestinian controls and present in 5/279388 alleles on gnomAD, all in heterozygotes.

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

From 3billion, SCV004013831.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

The homozygous variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). It is a stop-gained (nonsense) variant predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with PJVK -related disorder (ClinVar ID: VCV000560905 / PMID: 19888295). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Sep 29, 2024

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