NM_001127898.4(CLCN5):c.2297del (p.Met766fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 2, 2021
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:: RCV001954525.4

Allele description [Variation Report for NM_001127898.4(CLCN5):c.2297del (p.Met766fs)]

NM_001127898.4(CLCN5):c.2297del (p.Met766fs)

Genes:

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

Variant type:

Deletion

Cytogenetic location:

Xp11.23

Genomic location:

Preferred name:

NM_001127898.4(CLCN5):c.2297del (p.Met766fs)

HGVS:

NC_000023.11:g.50090823del
NG_007159.3:g.173208del
NM_000084.5:c.2087del
NM_001127898.4:c.2297delMANE SELECT
NM_001127899.4:c.2297del
NM_001282163.2:c.2147del
NP_000075.1:p.Met696fs
NP_001121370.1:p.Met766fs
NP_001121371.1:p.Met766fs
NP_001269092.1:p.Met716fs
NC_000023.10:g.49855480del

Protein change:

M696fs

Links:

dbSNP: rs2147607713

NCBI 1000 Genomes Browser:

rs2147607713

Molecular consequence:

NM_000084.5:c.2087del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127898.4:c.2297del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127899.4:c.2297del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282163.2:c.2147del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002196624	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 2, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22876375, 25907713, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002196624

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 2, 2021)

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

Dent Disease..

Lieske JC, Milliner DS, Beara-Lasic L, Harris P, Cogal A, Abrash E.

2012 Aug 9 [updated 2017 Dec 14]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.

PubMed [citation]

PMID:: 22876375

Mutation Update of the CLCN5 Gene Responsible for Dent Disease 1.

Mansour-Hendili L, Blanchard A, Le Pottier N, Roncelin I, Lourdel S, Treard C, González W, Vergara-Jaque A, Morin G, Colin E, Holder-Espinasse M, Bacchetta J, Baudouin V, Benoit S, Bérard E, Bourdat-Michel G, Bouchireb K, Burtey S, Cailliez M, Cardon G, Cartery C, Champion G, et al.

Hum Mutat. 2015 Aug;36(8):743-52. doi: 10.1002/humu.22804. Epub 2015 Jun 11. Review.

PubMed [citation]

PMID:: 25907713

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002196624.3

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

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with CLCN5-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Met696Argfs*4) in the CLCN5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLCN5 are known to be pathogenic (PMID: 22876375, 25907713).

#	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: Sep 29, 2024

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