NM_018941.4(CLN8):c.429_432del (p.Phe143fs) AND Neuronal ceroid lipofuscinosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 24, 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:: RCV001236145.5

Allele description [Variation Report for NM_018941.4(CLN8):c.429_432del (p.Phe143fs)]

NM_018941.4(CLN8):c.429_432del (p.Phe143fs)

Gene:

CLN8:CLN8 transmembrane ER and ERGIC protein [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

8p23.3

Genomic location:

Preferred name:

NM_018941.4(CLN8):c.429_432del (p.Phe143fs)

HGVS:

NC_000008.11:g.1771483_1771486del
NG_008656.2:g.20706_20709del
NM_018941.4:c.429_432delMANE SELECT
NP_061764.2:p.Phe143fs
LRG_691t1:c.429_432del
LRG_691:g.20706_20709del
NC_000008.10:g.1719646_1719649del
NC_000008.10:g.1719649_1719652del
NM_018941.3:c.429_432del

Protein change:

F143fs

Links:

dbSNP: rs759598033

NCBI 1000 Genomes Browser:

rs759598033

Molecular consequence:

NM_018941.4:c.429_432del - 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

Recent activity

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endonuclease III-like protein 1 isoform 1 [Homo sapiens]
endonuclease III-like protein 1 isoform 1 [Homo sapiens]
gi|1514769207|ref|NP_002519.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001408858	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 24, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15024724, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001408858

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 24, 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

Variant late infantile neuronal ceroid lipofuscinosis in a subset of Turkish patients is allelic to Northern epilepsy.

Ranta S, Topcu M, Tegelberg S, Tan H, Ustübütün A, Saatci I, Dufke A, Enders H, Pohl K, Alembik Y, Mitchell WA, Mole SE, Lehesjoki AE.

Hum Mutat. 2004 Apr;23(4):300-5.

PubMed [citation]

PMID:: 15024724

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, SCV001408858.4

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with CLN8-related conditions. ClinVar contains an entry for this variant (Variation ID: 962311). This variant is present in population databases (rs759598033, ExAC 0.001%). This sequence change creates a premature translational stop signal (p.Phe143Leufs*16) in the CLN8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLN8 are known to be pathogenic (PMID: 15024724).

#	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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