NM_006493.4(CLN5):c.838_841del (p.Gly280fs) AND Neuronal ceroid lipofuscinosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 2, 2020
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:: RCV001861806.6

Allele description [Variation Report for NM_006493.4(CLN5):c.838_841del (p.Gly280fs)]

NM_006493.4(CLN5):c.838_841del (p.Gly280fs)

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.838_841del (p.Gly280fs)

HGVS:

NC_000013.11:g.77000730_77000733del
NG_009064.1:g.13807_13810del
NM_001366624.2:c.*287_*290del
NM_006493.4:c.838_841delMANE SELECT
NP_006484.2:p.Gly280fs
LRG_692t1:c.985_988del
LRG_692:g.13807_13810del
NC_000013.10:g.77574864_77574867del
NC_000013.10:g.77574865_77574868del
NM_006493.2:c.985_988delGGAA

Protein change:

G280fs

Links:

dbSNP: rs1555274365

NCBI 1000 Genomes Browser:

rs1555274365

Molecular consequence:

NM_001366624.2:c.*287_*290del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_006493.4:c.838_841del - 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
SCV002231191	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 2, 2020)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 9662406, 20052765, 11971870, 24058541, 12134079, 24038957, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002231191

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 2, 2020)

germline

clinical testing

PubMed (7)
[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, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis.

Savukoski M, Klockars T, Holmberg V, Santavuori P, Lander ES, Peltonen L.

Nat Genet. 1998 Jul;19(3):286-8.

PubMed [citation]

PMID:: 9662406

The neuronal ceroid lipofuscinosis protein CLN5: new insights into cellular maturation, transport, and consequences of mutations.

Schmiedt ML, Bessa C, Heine C, Ribeiro MG, Jalanko A, Kyttälä A.

Hum Mutat. 2010 Mar;31(3):356-65. doi: 10.1002/humu.21195.

PubMed [citation]

PMID:: 20052765

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002231191.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the CLN5 protein. Other variant(s) that disrupt this region (p.Tyr392*) have been determined to be pathogenic (PMID: 9662406, 20052765, 11971870, 24058541, 24038957, 12134079, 24038957). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with CLN5-related conditions. ClinVar contains an entry for this variant (Variation ID: 555601). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gly329Thrfs*6) in the CLN5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 79 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: Sep 29, 2024

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