NM_006493.4(CLN5):c.812del (p.Asn271fs) AND Neuronal ceroid lipofuscinosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 16, 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:: RCV001386240.6

Allele description [Variation Report for NM_006493.4(CLN5):c.812del (p.Asn271fs)]

NM_006493.4(CLN5):c.812del (p.Asn271fs)

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.812del (p.Asn271fs)

HGVS:

NC_000013.11:g.77000704del
NG_009064.1:g.13781del
NM_001366624.2:c.*261del
NM_006493.4:c.812delMANE SELECT
NP_006484.2:p.Asn271fs
LRG_692:g.13781del
NC_000013.10:g.77574837del
NC_000013.10:g.77574839del

Protein change:

N271fs

Links:

dbSNP: rs2154035159

NCBI 1000 Genomes Browser:

rs2154035159

Molecular consequence:

NM_001366624.2:c.*261del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_006493.4:c.812del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001586381	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 16, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20157158, 20960652, 22532218, 25976102, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001586381

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 16, 2022)

germline

clinical testing

PubMed (5)
[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

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

Gene symbol: CLN5. Disease: Neuronal Ceroid Lipofuscinosis, finnish variant.

Kohan R, Cannelli N, Aiello C, Santorelli FM, Cismondi AI, Milà M, Oller Ramírez AM, Halac IN.

Hum Genet. 2008 Jun;123(5):552. No abstract available.

PubMed [citation]

PMID:: 20960652

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001586381.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the CLN5 protein in which other variant(s) (p.Lys368Serfs*15) have been determined to be pathogenic (PMID: 20157158, 20960652, 22532218, 25976102; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1073281). 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 creates a premature translational stop signal (p.Asn320Metfs*16) in the CLN5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 88 amino acid(s) of the CLN5 protein.

#	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: Feb 28, 2024

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