NM_006493.4(CLN5):c.524G>A (p.Trp175Ter) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Apr 16, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000187071.8

Allele description [Variation Report for NM_006493.4(CLN5):c.524G>A (p.Trp175Ter)]

NM_006493.4(CLN5):c.524G>A (p.Trp175Ter)

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.524G>A (p.Trp175Ter)

Other names:

p.W224*:TGG>TAG

HGVS:

NC_000013.11:g.76996086G>A
NG_009064.1:g.9163G>A
NM_001366624.2:c.524G>A
NM_006493.4:c.524G>AMANE SELECT
NP_001353553.1:p.Trp175Ter
NP_006484.2:p.Trp175Ter
LRG_692t1:c.671G>A
LRG_692:g.9163G>A
NC_000013.10:g.77570221G>A
NM_006493.2:c.671G>A
p.Trp224*

Protein change:

W175*

Links:

dbSNP: rs386833980

NCBI 1000 Genomes Browser:

rs386833980

Molecular consequence:

NM_001366624.2:c.524G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_006493.4:c.524G>A - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000240646	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (Jan 3, 2019)	germline	clinical testing	Citation Link,
SCV001713645	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 16, 2019)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 20157158, 21990111, 22727047, 23374165, 26342652, 25525159, 28542837, 29655203, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000240646

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(Jan 3, 2019)

germline

clinical testing

Citation Link,

SCV001713645

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 16, 2019)

germline

clinical testing

PubMed (9)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	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

Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses.

Kousi M, Lehesjoki AE, Mole SE.

Hum Mutat. 2012 Jan;33(1):42-63. doi: 10.1002/humu.21624. Epub 2011 Nov 16. Review.

PubMed [citation]

PMID:: 21990111

See all PubMed Citations (9)

Details of each submission

From GeneDx, SCV000240646.11

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

Description

A published W224X variant that is likely pathogenic has been identified in the CLN5 gene. The W224X nonsense variant in the CLN5 gene has been reported previously in three individuals with juvenile neuronal ceroid lipofuscinosis (NCL), who also harbored a second variant in the CLN5 gene, however phase was not established. (Xin et al., 2010; Starpoli et al., 2012). The W224X variant is predicted to cause loss of normal protein function through protein truncation. The W224X variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV001713645.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (9)

Description

PVS1, PS4_moderate, PM2, PP4

#	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		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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