NM_017882.3(CLN6):c.424dup (p.Tyr142fs) AND Neuronal ceroid lipofuscinosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 14, 2023
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:: RCV003649072.2

Allele description [Variation Report for NM_017882.3(CLN6):c.424dup (p.Tyr142fs)]

NM_017882.3(CLN6):c.424dup (p.Tyr142fs)

Gene:

CLN6:CLN6 transmembrane ER protein [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

15q23

Genomic location:

Preferred name:

NM_017882.3(CLN6):c.424dup (p.Tyr142fs)

HGVS:

NC_000015.10:g.68211737dup
NG_008764.2:g.50475dup
NG_131414.1:g.640dup
NM_001411068.1:c.520dup
NM_017882.3:c.424dupMANE SELECT
NP_001397997.1:p.Tyr174fs
NP_060352.1:p.Tyr142fs
LRG_832t1:c.424dup
LRG_832:g.50475dup
LRG_832p1:p.Tyr142fs
NC_000015.9:g.68504074_68504075insA
NC_000015.9:g.68504075dup

Protein change:

Y142fs

Molecular consequence:

NM_001411068.1:c.520dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_017882.3:c.424dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

RecName: Full=E3 ubiquitin-protein ligase RNF139; AltName: Full=RING finger prot...
RecName: Full=E3 ubiquitin-protein ligase RNF139; AltName: Full=RING finger protein 139; AltName: Full=RING-type E3 ubiquitin transferase RNF139; AltName: Full=Translocation in renal carcinoma on chromosome 8 protein
gi|74760542|sp|Q8WU17.1|RN139_HUMAN

Protein
RecName: Full=Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3; ...
RecName: Full=Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3; AltName: Full=Transducin beta chain 3
gi|121011|sp|P16520.1|GBB3_HUMAN

Protein
RecName: Full=Adhesion G protein-coupled receptor A2; AltName: Full=G-protein co...
RecName: Full=Adhesion G protein-coupled receptor A2; AltName: Full=G-protein coupled receptor 124; AltName: Full=Tumor endothelial marker 5; Flags: Precursor
gi|221222450|sp|Q96PE1.2|AGRA2_HUMA

Protein
RecName: Full=Protein Wnt-2; AltName: Full=Int-1-like protein 1; AltName: Full=I...
RecName: Full=Protein Wnt-2; AltName: Full=Int-1-like protein 1; AltName: Full=Int-1-related protein; Short=IRP; Flags: Precursor
gi|139750|sp|P09544.1|WNT2_HUMAN

Protein
RecName: Full=RPE-retinal G protein-coupled receptor
RecName: Full=RPE-retinal G protein-coupled receptor
gi|1350592|sp|P47804.1|RGR_HUMAN

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004551726	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 14, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19135028, 30561534, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004551726

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 14, 2023)

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

Citations

PubMed

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]

PMID:: 19135028

Kufs disease due to mutation of CLN6: clinical, pathological and molecular genetic features.

Berkovic SF, Oliver KL, Canafoglia L, Krieger P, Damiano JA, Hildebrand MS, Morbin M, Vears DF, Sofia V, Giuliano L, Garavaglia B, Simonati A, Santorelli FM, Gambardella A, Labate A, Belcastro V, Castellotti B, Ozkara C, Zeman A, Rankin J, Mole SE, Aguglia U, et al.

Brain. 2019 Jan 1;142(1):59-69. doi: 10.1093/brain/awy297.

PubMed [citation]

PMID:: 30561534

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004551726.1

#	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 creates a premature translational stop signal (p.Tyr142Leufs*9) in the CLN6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLN6 are known to be pathogenic (PMID: 19135028). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with CLN6-related conditions (PMID: 30561534). For these reasons, this variant has been classified as Pathogenic.

#	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

ClinVar

Relating variation to medicine