NM_006493.4(CLN5):c.83G>A (p.Trp28Ter) AND Neuronal ceroid lipofuscinosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 6, 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:: RCV001070707.6

Allele description [Variation Report for NM_006493.4(CLN5):c.83G>A (p.Trp28Ter)]

NM_006493.4(CLN5):c.83G>A (p.Trp28Ter)

Genes:

LOC130009913:ATAC-STARR-seq lymphoblastoid silent region 5414 [Gene]
CLN5:CLN5 intracellular trafficking protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q22.3

Genomic location:

Preferred name:

NM_006493.4(CLN5):c.83G>A (p.Trp28Ter)

HGVS:

NC_000013.11:g.76992181G>A
NG_009064.1:g.5258G>A
NM_001366624.2:c.83G>A
NM_006493.4:c.83G>AMANE SELECT
NP_001353553.1:p.Trp28Ter
NP_006484.2:p.Trp28Ter
LRG_692t1:c.230G>A
LRG_692:g.5258G>A
NC_000013.10:g.77566316G>A
NM_006493.2:c.230G>A

Protein change:

W28*

Links:

dbSNP: rs1242337070

NCBI 1000 Genomes Browser:

rs1242337070

Molecular consequence:

NM_001366624.2:c.83G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_006493.4:c.83G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

Recent activity

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YTH domain-containing protein [Caenorhabditis elegans]
YTH domain-containing protein [Caenorhabditis elegans]
gi|17543966|ref|NP_500287.1|

Protein
Caenorhabditis elegans Secreted protein (F46G11.2), mRNA
Caenorhabditis elegans Secreted protein (F46G11.2), mRNA
gi|1972306298|ref|NM_076571.8|

Nucleotide
Phenacobius mirabilis voucher UTEIC 44.11944 ectodermal-neural cortex 1-like pro...
Phenacobius mirabilis voucher UTEIC 44.11944 ectodermal-neural cortex 1-like protein (ENC1) gene, partial cds
gi|336051568|gb|JF949839.1|

Nucleotide
Mus musculus gasdermin A2 (Gsdma2), transcript variant 3, mRNA
Mus musculus gasdermin A2 (Gsdma2), transcript variant 3, mRNA
gi|1388876076|ref|NM_001363221.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001235974	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 6, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20157158, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001235974

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 6, 2021)

germline

clinical testing

PubMed (2)
[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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001235974.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Trp77*) in the CLN5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLN5 are known to be pathogenic (PMID: 20157158). This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CLN5-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.

#	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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