NM_001127898.4(CLCN5):c.1329dup (p.Asn444fs) AND Dent disease type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 24, 2018
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:: RCV001252964.2

Allele description [Variation Report for NM_001127898.4(CLCN5):c.1329dup (p.Asn444fs)]

NM_001127898.4(CLCN5):c.1329dup (p.Asn444fs)

Gene:

CLCN5:chloride voltage-gated channel 5 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

Xp11.23

Genomic location:

Preferred name:

NM_001127898.4(CLCN5):c.1329dup (p.Asn444fs)

HGVS:

NC_000023.11:g.50086642dup
NG_007159.3:g.169027dup
NM_000084.5:c.1119dup
NM_001127898.4:c.1329dupMANE SELECT
NM_001127899.4:c.1329dup
NM_001282163.2:c.1179dup
NP_000075.1:p.Asn374fs
NP_001121370.1:p.Asn444fs
NP_001121371.1:p.Asn444fs
NP_001269092.1:p.Asn394fs
NC_000023.10:g.49851299dup
NM_000084.4:c.1119dupC

Protein change:

N374fs

Links:

dbSNP: rs1933898062

NCBI 1000 Genomes Browser:

rs1933898062

Molecular consequence:

NM_000084.5:c.1119dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127898.4:c.1329dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127899.4:c.1329dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282163.2:c.1179dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Dent disease type 1
Synonyms:: NEPHROLITHIASIS, HYPERCALCIURIC, X-LINKED; Nephrolithiasis, hypercalciuria X-linked; Urolithiasis, hypercalciuric X-linked; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010225; MedGen: C1848336; Orphanet: 1652; Orphanet: 93622; OMIM: 300009

Recent activity

Clear Turn Off Turn On

mKIAA1019 protein, partial [Mus musculus]
mKIAA1019 protein, partial [Mus musculus]
gi|28972568|dbj|BAC65700.1|

Protein
AGENCOURT_87408658 NICHD_XGC_bone Xenopus laevis cDNA clone IMAGE:8740740 3', mR...
AGENCOURT_87408658 NICHD_XGC_bone Xenopus laevis cDNA clone IMAGE:8740740 3', mRNA sequence
gi|111605244|gnl|dbEST|40946010|gb| 539.1|

Nucleotide
CBTC1752.rev NICHD_XGC_tropBone1 Xenopus tropicalis cDNA clone IMAGE:8934176 3',...
CBTC1752.rev NICHD_XGC_tropBone1 Xenopus tropicalis cDNA clone IMAGE:8934176 3', mRNA sequence
gi|126262061|gnl|dbEST|45035725|gb| 173.1|

Nucleotide
JGI_CAAM9552.rev NIH_XGC_tropTe3 Xenopus tropicalis cDNA clone IMAGE:7683326 3',...
JGI_CAAM9552.rev NIH_XGC_tropTe3 Xenopus tropicalis cDNA clone IMAGE:7683326 3', mRNA sequence
gi|58640484|gnl|dbEST|27608059|gb|C 40.1|

Nucleotide
JGI_CAAM9552.fwd NIH_XGC_tropTe3 Xenopus tropicalis cDNA clone IMAGE:7683326 5',...
JGI_CAAM9552.fwd NIH_XGC_tropTe3 Xenopus tropicalis cDNA clone IMAGE:7683326 5', mRNA sequence
gi|58640485|gnl|dbEST|27608060|gb|C 41.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001427205	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 24, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001427205

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 24, 2018)

unknown

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV001427205.2

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

Description

A hemizygous duplication variant, NM_000084.4(CLCN5):c.1119dupC, has been identified in exon 8 of 12 of the CLCN5 gene. This duplication is predicted to create a frameshift starting at amino acid position 374, introducing a stop codon two residues downstream (NP_000075.1(CLCN5):p. (Asn374Glnfs*2)). This variant is predicted to result in loss of protein function through nonsense mediated decay, which is a reported mechanism of pathogenicity for this gene. The variant is absent in population databases (gnomAD, dbSNP, 1000G) and has not been previously reported in clinical cases. However, many other upstream and downstream loss of function variants have been reported pathogenic (ClinVar). Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.

#	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		not provided	not provided	not provided	not provided

Last Updated: Jul 29, 2023

ClinVar

Relating variation to medicine