NM_001127898.4(CLCN5):c.2119C>T (p.Arg707Ter) AND Proteinuria, low molecular weight, with hypercalciuria and nephrocalcinosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 5, 2022
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:: RCV001813768.2

Allele description [Variation Report for NM_001127898.4(CLCN5):c.2119C>T (p.Arg707Ter)]

NM_001127898.4(CLCN5):c.2119C>T (p.Arg707Ter)

Genes:

LOC126863258:BRD4-independent group 4 enhancer GRCh37_chrX:49854497-49855696 [Gene]
CLCN5:chloride voltage-gated channel 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp11.23

Genomic location:

Preferred name:

NM_001127898.4(CLCN5):c.2119C>T (p.Arg707Ter)

HGVS:

NC_000023.11:g.50090490C>T
NG_007159.3:g.172875C>T
NM_000084.5:c.1909C>T
NM_001127898.4:c.2119C>TMANE SELECT
NM_001127899.4:c.2119C>T
NM_001282163.2:c.1969C>T
NP_000075.1:p.Arg637Ter
NP_001121370.1:p.Arg707Ter
NP_001121371.1:p.Arg707Ter
NP_001269092.1:p.Arg657Ter
NC_000023.10:g.49855147C>T
NM_000084.2:c.1909C>T
p.R637Ter

Protein change:

R637*

Links:

dbSNP: rs797044813

NCBI 1000 Genomes Browser:

rs797044813

Molecular consequence:

NM_000084.5:c.1909C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001127898.4:c.2119C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001127899.4:c.2119C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001282163.2:c.1969C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Proteinuria, low molecular weight, with hypercalciuria and nephrocalcinosis
Identifiers:: MONDO: MONDO:0010644; MedGen: C1839874; Orphanet: 1652; Orphanet: 93622; OMIM: 308990

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002061229	DASA	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 5, 2022)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 11136179, 15719255, 15895257, 16822791, 18038239, 19076289, 19546586, 24081861, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002061229

DASA

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 5, 2022)

germline

clinical testing

PubMed (9)
[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	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of two novel mutations in the CLCN5 gene in Japanese patients with familial idiopathic low molecular weight proteinuria (Japanese Dent's disease).

Takemura T, Hino S, Ikeda M, Okada M, Igarashi T, Inatomi J, Yoshioka K.

Am J Kidney Dis. 2001 Jan;37(1):138-143.

PubMed [citation]

PMID:: 11136179

Phenotype and genotype of Dent's disease in three Korean boys.

Cheong HI, Lee JW, Zheng SH, Lee JH, Kang JH, Kang HG, Ha IS, Lee SJ, Choi Y.

Pediatr Nephrol. 2005 Apr;20(4):455-9. Epub 2005 Feb 18.

PubMed [citation]

PMID:: 15719255

See all PubMed Citations (9)

Details of each submission

From DASA, SCV002061229.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (9)

Description

The c.1909C>T;p.(Arg637*) variant creates a premature translational stop signal in the CLCN5 gene. It is expected to result in an absent or disrupted protein product -PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant(Clinvar ID: 207999; PMID: 11136179; 15719255; 15895257; 16822791; 18038239; 19076289; 19546586; 24081861) - PS4.The variant was observed to have arisen de novo (paternity confirmed) in a patient with the disease and no family history(PMID: 11136179; 15719255) - PS2. This variant is not present in population databases (rs797044813, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. The variant co-segregated with disease in multiple affected family members (PMID: 19076289; 19546586) - PP1_supporting. In summary, the currently available evidence indicates that the variant is pathogenic.

#	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		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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