VCV002841702.5 - ClinVar

NM_001080414.4(CCDC88C):c.1702C>T (p.Arg568Ter)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (2)

2 out of 3 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001080414.4(CCDC88C):c.1702C>T (p.Arg568Ter)

Variation ID: 2841702 Accession: VCV002841702.5

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 14q32.11 14: 91314114 (GRCh38) [ NCBI UCSC ] 14: 91780458 (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 20, 2024	Oct 10, 2026	Mar 30, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001080414.4:c.1702C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001073883.2:p.Arg568Ter	nonsense
NR_189158.1:n.1832C>T
NR_189159.1:n.1832C>T
NC_000014.9:g.91314114G>A
NC_000014.8:g.91780458G>A
NG_033118.2:g.108731C>T

... more HGVS ... less HGVS

Protein change

R568*

Other names

Canonical SPDI

NC_000014.9:91314113:G:A

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.

The Genome Aggregation Database (gnomAD), exomes 0.00000

The Genome Aggregation Database (gnomAD) 0.00001

Exome Aggregation Consortium (ExAC) 0.00002

Links

ClinGen: CA7309836 dbSNP: rs777488098 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.
CCDC88C		-	-	GRCh38 GRCh37	1974	2029

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.
not provided	Pathogenic (1)	criteria provided, single submitter	Feb 25, 2024	RCV003721104.4
Spinocerebellar ataxia type 40	Likely pathogenic (1)	no assertion criteria provided	Jun 1, 2022	RCV004765940.2
Hydrocephalus, nonsyndromic, autosomal recessive 1	Pathogenic (1)	criteria provided, single submitter	Mar 30, 2025	RCV007087553.1

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.	Expand all rows Collapse all rows 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 (Feb 25, 2024) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004502123.3 First in ClinVar: Feb 20, 2024 Last updated: Feb 23, 2026	Publications: PubMed (2) PubMed: 23042809‚ 29225145 Comment: show This sequence change creates a premature translational stop signal (p.Arg568*) in the CCDC88C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CCDC88C are known to be pathogenic (PMID: 23042809, 29225145). This variant is present in population databases (rs777488098, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with hydrocephalus (PMID: 29225145). For these reasons, this variant has been classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Mar 30, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Hydrocephalus, nonsyndromic, autosomal recessive 1	Myriad Genetics, Inc. Accession: SCV008090473.1 First in ClinVar: Oct 10, 2026 Last updated: Oct 10, 2026	Comment: show NM_001080414.3(CCDC88C):c.1702C>T(R568*) is expected to be pathogenic in the context of congenital hydrocephalus, CCDC88C-related. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in CCDC88C, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening. (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Likely pathogenic (Jun 01, 2022) N Not contributing to aggregate classification	no assertion criteria provided	Spinocerebellar ataxia type 40	Solve-RD Consortium Accession: SCV005091503.1 First in ClinVar: Oct 26, 2024 Last updated: Oct 26, 2024 Comment: Variant identified during reanalysis of unsolved cases by the Solve-RD project. The Solve-RD project has received funding from the European Union’s Horizon 2020 research and … (more) Variant identified during reanalysis of unsolved cases by the Solve-RD project. The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 779257. (less)	Publications: PubMed (1) PubMed: 39825153 Comment: show Variant confirmed as disease-causing by referring clinical team (less) Observation: 1 Collection method: provider interpretation Allele origin: inherited Affected status: yes Observation 1 Collection method: provider interpretation Allele origin: inherited Affected status: yes

Comment:

This sequence change creates a premature translational stop signal (p.Arg568*) in the CCDC88C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CCDC88C are known to be pathogenic (PMID: 23042809, 29225145). This variant is present in population databases (rs777488098, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with hydrocephalus (PMID: 29225145). For these reasons, this variant has been classified as Pathogenic.

Comment:

NM_001080414.3(CCDC88C):c.1702C>T(R568*) is expected to be pathogenic in the context of congenital hydrocephalus, CCDC88C-related. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in CCDC88C, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.	Laurie S	Nature medicine	2025	PMID: 39825153
Surprisingly good outcome in antenatal diagnosis of severe hydrocephalus related to CCDC88C deficiency.	Wallis M	European journal of medical genetics	2018	PMID: 29225145
Two novel CCDC88C mutations confirm the role of DAPLE in autosomal recessive congenital hydrocephalus.	Drielsma A	Journal of medical genetics	2012	PMID: 23042809

Text-mined citations for rs777488098 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 10, 2026