VCV003233661.2 - ClinVar

NM_017882.3(CLN6):c.829_836delinsCCT (p.Val277fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_017882.3(CLN6):c.829_836delinsCCT (p.Val277fs)

Variation ID: 3233661 Accession: VCV003233661.2

Type and length

Indel, 8 bp

Location

Cytogenetic: 15q23 15: 68208240-68208247 (GRCh38) [ NCBI UCSC ] 15: 68500578-68500585 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	May 8, 2024	Jul 7, 2024	Mar 4, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_017882.3:c.829_836delinsCCT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_060352.1:p.Val277fs	frameshift
NM_001411068.1:c.925_932delinsCCT	NP_001397997.1:p.Val309fs	frameshift
NC_000015.10:g.68208240_68208247delinsAGG
NC_000015.9:g.68500578_68500585delinsAGG
NG_008764.2:g.53965_53972delinsCCT
LRG_832:g.53965_53972delinsCCT
LRG_832t1:c.829_836delinsCCT	LRG_832p1:p.Val277fs

... more HGVS ... less HGVS

Protein change

V277fs, V309fs

Other names

Canonical SPDI

NC_000015.10:68208239:CAGGCGAC:AGG

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CLN6		-	-	GRCh38 GRCh37	766	782

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Neuronal ceroid lipofuscinosis	Pathogenic (1)	criteria provided, single submitter	Mar 4, 2024	RCV004526511.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Mar 04, 2024)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Neuronal ceroid lipofuscinosis Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV005040409.2 First in ClinVar: May 07, 2024 Last updated: Jul 07, 2024	Publications: PubMed (2) PubMed: 34440436‚ 35505348 Comment: Variant summary: CLN6 c.829_836delinsCCT (p.Val277ProfsX5) results in a premature termination codon, although it is not expected to result in NMD it is predicted to cause … (more) Variant summary: CLN6 c.829_836delinsCCT (p.Val277ProfsX5) results in a premature termination codon, although it is not expected to result in NMD it is predicted to cause a truncation of the encoded protein which is a commonly known mechanism for disease. The variant was absent in 251388 control chromosomes. c.829_836delinsCCT has been reported in the literature in individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) (Barbosa-Gouveia_2021, Rus_2022). Additionally, variants downstream have been classified on the pathogenic spectrum internally and in ClinVar. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 34440436, 35505348). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic. (less)

Comment:

Variant summary: CLN6 c.829_836delinsCCT (p.Val277ProfsX5) results in a premature termination codon, although it is not expected to result in NMD it is predicted to cause a truncation of the encoded protein which is a commonly known mechanism for disease. The variant was absent in 251388 control chromosomes. c.829_836delinsCCT has been reported in the literature in individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) (Barbosa-Gouveia_2021, Rus_2022). Additionally, variants downstream have been classified on the pathogenic spectrum internally and in ClinVar. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 34440436, 35505348). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Clinical and genetic characterization of a cohort of 97 CLN6 patients tested at a single center.	Rus CM	Orphanet journal of rare diseases	2022	PMID: 35505348
Utility of Gene Panels for the Diagnosis of Inborn Errors of Metabolism in a Metabolic Reference Center.	Barbosa-Gouveia S	Genes	2021	PMID: 34440436

Text-mined citations for this variant ...

Record last updated Jul 07, 2024

ClinVar Genomic variation as it relates to human health

NM_017882.3(CLN6):c.829_836delinsCCT (p.Val277fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...