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NM_017882.3(CLN6):c.767A>G (p.Asp256Gly) AND Neuronal ceroid lipofuscinosis

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 27, 2024
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:
RCV001037728.7

Allele description

NM_017882.3(CLN6):c.767A>G (p.Asp256Gly)

Gene:
CLN6:CLN6 transmembrane ER protein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q23
Genomic location:
Preferred name:
NM_017882.3(CLN6):c.767A>G (p.Asp256Gly)
Other names:
p.D256G:GAC>GGC
HGVS:
  • NC_000015.10:g.68208309T>C
  • NG_008764.2:g.53903A>G
  • NM_017882.3:c.767A>GMANE SELECT
  • NP_060352.1:p.Asp256Gly
  • LRG_832t1:c.767A>G
  • LRG_832:g.53903A>G
  • LRG_832p1:p.Asp256Gly
  • NC_000015.9:g.68500647T>C
  • NM_017882.2:c.767A>G
Protein change:
D256G
Links:
dbSNP: rs143781303
NCBI 1000 Genomes Browser:
rs143781303
Molecular consequence:
  • NM_017882.3:c.767A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Neuronal ceroid lipofuscinosis
Synonyms:
Ceroid storage disease
Identifiers:
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)
OriginMethodCitations
SCV001201156Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Jan 27, 2024)
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

Citations

PubMed

Mutation of the CLN6 gene in teenage-onset progressive myoclonus epilepsy.

Andrade DM, Paton T, Turnbull J, Marshall CR, Scherer SW, Minassian BA.

Pediatr Neurol. 2012 Sep;47(3):205-8. doi: 10.1016/j.pediatrneurol.2012.05.004.

PubMed [citation]
PMID:
22883287

Novel mutations in typical and atypical genetic loci through exome sequencing in autosomal recessive cerebellar ataxia families.

Faruq M, Narang A, Kumari R, Pandey R, Garg A, Behari M, Dash D, Srivastava AK, Mukerji M.

Clin Genet. 2014 Oct;86(4):335-41. doi: 10.1111/cge.12279. Epub 2013 Oct 13.

PubMed [citation]
PMID:
24102492
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001201156.5

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

Description

This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 256 of the CLN6 protein (p.Asp256Gly). This variant is present in population databases (rs143781303, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CLN6-related conditions. ClinVar contains an entry for this variant (Variation ID: 205177). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CLN6 protein function. This variant disrupts the p.Asp256 amino acid residue in CLN6. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22883287, 24102492). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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

Last Updated: Feb 20, 2024