NM_018941.3(CLN8):c.562_563delCT AND Neuronal ceroid lipofuscinosis 8

Clinical significance:Likely pathogenic (Last evaluated: May 14, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000050126.3

Allele description [Variation Report for NM_018941.3(CLN8):c.562_563delCT]

NM_018941.4(CLN8):c.562_563del (p.Leu188fs)

Gene:
CLN8:CLN8 transmembrane ER and ERGIC protein [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
8p23.3
Genomic location:
Preferred name:
NM_018941.4(CLN8):c.562_563del (p.Leu188fs)
HGVS:
  • NC_000008.11:g.1780266CT[1]
  • NG_008656.2:g.29489CT[1]
  • NM_018941.4:c.562_563delMANE SELECT
  • NP_061764.2:p.Leu188fs
  • LRG_691:g.29489CT[1]
  • NC_000008.10:g.1728431_1728432del
  • NC_000008.10:g.1728432CT[1]
  • NM_018941.3:c.562_563delCT
Protein change:
L188fs
Links:
dbSNP: rs386834132
NCBI 1000 Genomes Browser:
rs386834132
Molecular consequence:
  • NM_018941.4:c.562_563del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Neuronal ceroid lipofuscinosis 8 (CLN8)
Synonyms:
Northern epilepsy; CLN8-Related Neuronal Ceroid-Lipofuscinosis
Identifiers:
MONDO: MONDO:0010830; MedGen: C1838570; Orphanet: 168491; Orphanet: 228354; Orphanet: 79264; OMIM: 600143

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000082536Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)no assertion criteria providedprobable-pathogenicnot providednot provided

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

SCV000220700Counsylcriteria provided, single submitter
Likely pathogenic
(Sep 16, 2014)
unknownliterature only

PubMed (3)
[See all records that cite these PMIDs]

Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015),

Citation Link,

SCV001623276Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(May 14, 2021)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Description

FinDis database variant: This variant was not found or characterized by our laboratory, data were collected from public sources: see reference

SCV000082536

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providednot providednot providednot providednot providednot provided1not providedliterature only
not providedunknownunknownnot providednot providednot providednot providednot providedliterature only

Citations

PubMed

The neuronal ceroid lipofuscinosis CLN8 membrane protein is a resident of the endoplasmic reticulum.

Lonka L, Kyttälä A, Ranta S, Jalanko A, Lehesjoki AE.

Hum Mol Genet. 2000 Jul 1;9(11):1691-7.

PubMed [citation]
PMID:
10861296

Localization of wild-type and mutant neuronal ceroid lipofuscinosis CLN8 proteins in non-neuronal and neuronal cells.

Lonka L, Salonen T, Siintola E, Kopra O, Lehesjoki AE, Jalanko A.

J Neurosci Res. 2004 Jun 15;76(6):862-71.

PubMed [citation]
PMID:
15160397
See all PubMed Citations (5)

Details of each submission

From Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM), SCV000082536.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providednot provided PubMed (1)

Description

Converted during submission to Likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1not providednot provided1not providednot providednot providednot providednot providednot provided

From Counsyl, SCV000220700.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001623276.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: CLN8 c.562_563delCT (p.Leu188ValfsX58) results in a premature termination codon located in the last exon therefore it is not expected to elicit nonsense mediated decay, but is predicted to cause a truncation of the encoded protein. Truncations downstream of this position have been reported in affected individuals (HGMD). The variant allele was found at a frequency of 4e-06 in 250252 control chromosomes (gnomAD). The variant, c.562_563delCT, or the equivalent protein level change (p.Leu188Valfs), has been reported in the literature in individuals affected with Neuronal Ceroid-Lipofuscinosis, CLN8-Related (Allen_2012, Lee_2014). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 12, 2022

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