NM_017882.3(CLN6):c.543-2A>G AND Neuronal ceroid lipofuscinosis

Clinical significance:Likely pathogenic (Last evaluated: Jan 7, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_017882.3(CLN6):c.543-2A>G]


CLN6:CLN6 transmembrane ER protein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
  • NC_000015.10:g.68209761T>C
  • NG_008764.2:g.52451A>G
  • NM_017882.3:c.543-2A>GMANE SELECT
  • LRG_832t1:c.543-2A>G
  • LRG_832:g.52451A>G
  • NC_000015.9:g.68502099T>C
Molecular consequence:
  • NM_017882.3:c.543-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]


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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001574429Invitaecriteria provided, single submitter
Likely pathogenic
(Jan 7, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

Variant late infantile ceroid lipofuscinoses associated with novel mutations in CLN6.

Cannelli N, Garavaglia B, Simonati A, Aiello C, Barzaghi C, Pezzini F, Cilio MR, Biancheri R, Morbin M, Dalla Bernardina B, Granata T, Tessa A, Invernizzi F, Pessagno A, Boldrini R, Zibordi F, Grazian L, Claps D, Carrozzo R, Mole SE, Nardocci N, Santorelli FM.

Biochem Biophys Res Commun. 2009 Feb 20;379(4):892-7. doi: 10.1016/j.bbrc.2008.12.159. Epub 2009 Jan 7.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001574429.1

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


This sequence change affects an acceptor splice site in intron 5 of the CLN6 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CLN6-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CLN6 are known to be pathogenic (PMID: 19135028). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Oct 7, 2021

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