NM_006493.4(CLN5):c.713_720del (p.Thr238fs) AND Neuronal ceroid lipofuscinosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 28, 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:: RCV001855490.6

Allele description [Variation Report for NM_006493.4(CLN5):c.713_720del (p.Thr238fs)]

NM_006493.4(CLN5):c.713_720del (p.Thr238fs)

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.713_720del (p.Thr238fs)

HGVS:

NC_000013.11:g.77000605_77000612del
NG_009064.1:g.13682_13689del
NM_001366624.2:c.*162_*169del
NM_006493.4:c.713_720delMANE SELECT
NP_006484.2:p.Thr238fs
LRG_692t1:c.860_867del
LRG_692t1:c.860_867del8
LRG_692:g.13682_13689del
NC_000013.10:g.77574740_77574747del
NM_006493.2:c.860_867del8

Protein change:

T238fs

Links:

dbSNP: rs1555274344

NCBI 1000 Genomes Browser:

rs1555274344

Molecular consequence:

NM_001366624.2:c.*162_*169del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_006493.4:c.713_720del - 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
SCV002148046	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 28, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002148046

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 28, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV002148046.3

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

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.Phe325Trpfs*26) have been determined to be pathogenic (Invitae). 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: 552578). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Thr287Lysfs*4) in the CLN5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 121 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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