NM_006493.4(CLN5):c.340-1del AND Neuronal ceroid lipofuscinosis

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 30, 2023
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:: RCV003532090.2

Allele description [Variation Report for NM_006493.4(CLN5):c.340-1del]

NM_006493.4(CLN5):c.340-1del

Gene:

CLN5:CLN5 intracellular trafficking protein [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

13q22.3

Genomic location:

Preferred name:

NM_006493.4(CLN5):c.340-1del

HGVS:

NC_000013.11:g.76995901del
NG_009064.1:g.8978del
NM_001366624.2:c.340-1del
NM_006493.4:c.340-1delMANE SELECT
LRG_692t1:c.487-1del
LRG_692:g.8978del
NC_000013.10:g.77570036del
NM_006493.2:c.487-1delG

Links:

dbSNP: rs1057516390

NCBI 1000 Genomes Browser:

rs1057516390

Molecular consequence:

NM_001366624.2:c.340-1del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_006493.4:c.340-1del - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Neuronal ceroid lipofuscinosis
Synonyms:: Ceroid storage disease
Identifiers:: MONDO: MONDO:0016295; MedGen: C0027877; Orphanet: 79263; OMIM: PS256730

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004270373	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 30, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16199547, 20157158, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004270373

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 30, 2023)

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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

CLN5 mutations are frequent in juvenile and late-onset non-Finnish patients with NCL.

Xin W, Mullen TE, Kiely R, Min J, Feng X, Cao Y, O'Malley L, Shen Y, Chu-Shore C, Mole SE, Goebel HH, Sims K.

Neurology. 2010 Feb 16;74(7):565-71. doi: 10.1212/WNL.0b013e3181cff70d.

PubMed [citation]

PMID:: 20157158

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004270373.1

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 370310). This variant has not been reported in the literature in individuals affected with CLN5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a splice site in intron 2 of the CLN5 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CLN5 are known to be pathogenic (PMID: 20157158).

#	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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