VCV002762841.1 - ClinVar

NM_014956.5(CEP164):c.349_352del (p.Glu117fs)

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_014956.5(CEP164):c.349_352del (p.Glu117fs)

Variation ID: 2762841 Accession: VCV002762841.1

Type and length

Deletion, 4 bp

Location

Cytogenetic: 11q23.3 11: 117351944-117351947 (GRCh38) [ NCBI UCSC ] 11: 117222660-117222663 (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	Feb 14, 2024	Feb 14, 2024	Jan 12, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_014956.5:c.349_352del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_055771.4:p.Glu117fs	frameshift
NM_001271933.2:c.349_352del	NP_001258862.1:p.Glu117fs	frameshift
NC_000011.10:g.117351944_117351947del
NC_000011.9:g.117222660_117222663del
NG_033032.1:g.35167_35170del

... more HGVS ... less HGVS

Protein change

E117fs

Other names

Canonical SPDI

NC_000011.10:117351943:GAAA:

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

ClinGen: CA2697558982 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.
CEP164		-	-	GRCh38 GRCh37	1383	1415

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.
Nephronophthisis 15	Pathogenic (1)	criteria provided, single submitter	Jan 12, 2024	RCV003532399.2

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 (Jan 12, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Nephronophthisis 15 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004325390.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024	Publications: PubMed (5) PubMed: 22863007‚ 28125082‚ 32367404‚ 34132027‚ 34499853 Comment: This sequence change creates a premature translational stop signal (p.Glu117Argfs20) in the CEP164 gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Glu117Argfs20) in the CEP164 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP164 are known to be pathogenic (PMID: 22863007, 28125082, 32367404, 34132027, 34499853). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CEP164-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)

Comment:

This sequence change creates a premature translational stop signal (p.Glu117Argfs*20) in the CEP164 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP164 are known to be pathogenic (PMID: 22863007, 28125082, 32367404, 34132027, 34499853). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CEP164-related conditions. For these reasons, this variant has been 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
Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathies.	Rosa E Silva I	Structure (London, England : 1993)	2022	PMID: 34499853
Expanding the genetic landscape of oral-facial-digital syndrome with two novel genes.	Strong A	American journal of medical genetics. Part A	2021	PMID: 34132027
An exome-first approach to aid in the diagnosis of primary ciliary dyskinesia.	Shamseldin HE	Human genetics	2020	PMID: 32367404
Molecular genetic findings and clinical correlations in 100 patients with Joubert syndrome and related disorders prospectively evaluated at a single center.	Vilboux T	Genetics in medicine : official journal of the American College of Medical Genetics	2017	PMID: 28125082
Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling.	Chaki M	Cell	2012	PMID: 22863007

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NM_014956.5(CEP164):c.349_352del (p.Glu117fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...