NM_018941.4(CLN8):c.792C>G (p.Asn264Lys) AND Neuronal ceroid lipofuscinosis

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Sep 1, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000988030.5

Allele description [Variation Report for NM_018941.4(CLN8):c.792C>G (p.Asn264Lys)]

NM_018941.4(CLN8):c.792C>G (p.Asn264Lys)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

8p23.3

Genomic location:

Preferred name:

NM_018941.4(CLN8):c.792C>G (p.Asn264Lys)

HGVS:

NC_000008.11:g.1780498C>G
NG_008656.2:g.29721C>G
NM_018941.4:c.792C>GMANE SELECT
NP_061764.2:p.Asn264Lys
NP_061764.2:p.Asn264Lys
LRG_691t1:c.792C>G
LRG_691:g.29721C>G
LRG_691p1:p.Asn264Lys
NC_000008.10:g.1728664C>G
NM_018941.3:c.792C>G

Protein change:

N264K

Links:

dbSNP: rs587779411

NCBI 1000 Genomes Browser:

rs587779411

Molecular consequence:

NM_018941.4:c.792C>G - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

no known functional consequence

Condition(s)

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

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D007485 (1)
MeSH
Ioxaglic Acid
Ioxaglic Acid
A low-osmolar, ionic contrast medium used in various radiographic procedures.<br/>Year introduced: 1987

MeSH
Homo sapiens SEC31 homolog B, COPII coat complex component (SEC31B), mRNA
Homo sapiens SEC31 homolog B, COPII coat complex component (SEC31B), mRNA
gi|1519315087|ref|NM_015490.4|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001137579	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Likely pathogenic (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV002162739	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24767253, 30741402, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001137579

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Likely pathogenic
(May 28, 2019)

unknown

clinical testing

Citation Link,

SCV002162739

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2022)

germline

clinical testing

PubMed (3)
[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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders.

Fernández-Marmiesse A, Morey M, Pineda M, Eiris J, Couce ML, Castro-Gago M, Fraga JM, Lacerda L, Gouveia S, Pérez-Poyato MS, Armstrong J, Castiñeiras D, Cocho JA.

Orphanet J Rare Dis. 2014 Apr 25;9:59. doi: 10.1186/1750-1172-9-59.

PubMed [citation]

PMID:: 24767253
PMCID:: PMC4024120

Congenital CLN8 disease of neuronal ceroid lipofuscinosis: a novel phenotype.

Pesaola F, Kohan R, Cismondi IA, Guelbert N, Pons P, Oller-Ramirez AM, Noher de Halac I.

Rev Neurol. 2019 Feb 16;68(4):155-159. Spanish, English.

PubMed [citation]

PMID:: 30741402

See all PubMed Citations (3)

Details of each submission

From Mendelics, SCV001137579.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002162739.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 264 of the CLN8 protein (p.Asn264Lys). This variant is present in population databases (rs587779411, gnomAD 0.007%). This missense change has been observed in individual(s) with CLN8-related conditions (PMID: 24767253, 30741402). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 100736). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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