ClinVar Genomic variation as it relates to human health
NM_001378615.1(CC2D2A):c.3364C>T (p.Pro1122Ser)
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.
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(2); Likely pathogenic(4); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001378615.1(CC2D2A):c.3364C>T (p.Pro1122Ser)
Variation ID: 743 Accession: VCV000000743.32
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 4p15.32 4: 15567752 (GRCh38) [ NCBI UCSC ] 4: 15569375 (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 Nov 9, 2015 Apr 6, 2024 Mar 17, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001378615.1:c.3364C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001365544.1:p.Pro1122Ser missense NM_001080522.2:c.3364C>T NP_001073991.2:p.Pro1122Ser missense NM_001378617.1:c.3217C>T NP_001365546.1:p.Pro1073Ser missense NC_000004.12:g.15567752C>T NC_000004.11:g.15569375C>T NG_013035.1:g.102887C>T LRG_697:g.102887C>T LRG_697t1:c.3364C>T LRG_697p1:p.Pro1122Ser Q9P2K1:p.Pro1122Ser - Protein change
- P1122S, P1073S
- Other names
- -
- Canonical SPDI
- NC_000004.12:15567751:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe 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
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 | ||
---|---|---|---|---|---|---|
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. |
|||
CC2D2A | - | - |
GRCh38 GRCh37 |
2008 | 2062 |
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. |
---|---|---|---|---|
Conflicting interpretations of pathogenicity (6) |
criteria provided, conflicting classifications
|
Mar 17, 2024 | RCV000000779.12 | |
Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
May 17, 2022 | RCV000730543.10 | |
Likely pathogenic (1) |
criteria provided, single submitter
|
Nov 14, 2019 | RCV001329602.4 | |
Pathogenic (1) |
criteria provided, single submitter
|
Mar 10, 2022 | RCV001851514.6 |
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
(Feb 23, 2015)
|
criteria provided, single submitter
Method: research
|
Joubert syndrome 9
Affected status: yes
Allele origin:
unknown
|
UW Hindbrain Malformation Research Program, University of Washington
Additional submitter:
University of Washington Center for Mendelian Genomics, University of Washington
Accession: SCV000256330.1
First in ClinVar: Nov 09, 2015 Last updated: Nov 09, 2015 |
|
|
Likely pathogenic
(May 17, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV003820484.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
|
|
Pathogenic
(Mar 10, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Familial aplasia of the vermis
Meckel-Gruber syndrome
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV002237108.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 28, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, … (more)
For these reasons, this variant has been classified as Pathogenic. 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) performed at Invitae indicates that this missense variant is expected to disrupt CC2D2A protein function. ClinVar contains an entry for this variant (Variation ID: 743). This missense change has been observed in individual(s) with Joubert syndrome (PMID: 18950740). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs118204051, gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1122 of the CC2D2A protein (p.Pro1122Ser). (less)
|
|
Likely pathogenic
(Nov 28, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000858288.1
First in ClinVar: Dec 16, 2018 Last updated: Dec 16, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
Uncertain significance
(Dec 03, 2018)
|
criteria provided, single submitter
Method: research
|
Joubert syndrome 9
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001164435.1
First in ClinVar: Mar 01, 2020 Last updated: Mar 01, 2020 |
Comment:
The homozygous p.Pro1122Ser variant in CC2D2A was identified by our study in one individual with Joubert syndrome. The p.Pro1122Ser variant in CC2D2A has been reported … (more)
The homozygous p.Pro1122Ser variant in CC2D2A was identified by our study in one individual with Joubert syndrome. The p.Pro1122Ser variant in CC2D2A has been reported in at least 5 Saudi Arabian individuals with Joubert syndrome (PMID: 26092869, 18950740), and has been identified in 0.01951% (1/5126) of other chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although there is some suspicion of pathogenicity, the clinical significance of the p.Pro1122Ser variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3, PM1_Supporting (Richards 2015). (less)
|
|
Likely pathogenic
(Nov 14, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
COACH syndrome 1
Affected status: yes
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV001521087.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing by following sources … (more)
This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing by following sources [PMID: 29620724, 18950740, ClinVar ID: 743] (less)
|
|
Likely pathogenic
(Mar 17, 2024)
|
criteria provided, single submitter
Method: research
|
Joubert syndrome 9
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004804917.2
First in ClinVar: Mar 30, 2024 Last updated: Apr 06, 2024 |
|
|
Pathogenic
(Nov 01, 2008)
|
no assertion criteria provided
Method: literature only
|
JOUBERT SYNDROME 9
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000020929.2
First in ClinVar: Apr 04, 2013 Last updated: Feb 02, 2017 |
Comment on evidence:
In 2 patients from 2 different consanguineous Saudi Arabian families with Joubert syndrome (JBTS9; 612285), Gorden et al. (2008) identified a homozygous 3364C-T transition in … (more)
In 2 patients from 2 different consanguineous Saudi Arabian families with Joubert syndrome (JBTS9; 612285), Gorden et al. (2008) identified a homozygous 3364C-T transition in the CC2D2A gene, resulting in a pro1122-to-ser (P1122S) substitution. Both patients had the molar tooth sign on brain MRI, but only 1 had additional features, including retinal dystrophy, and hepatosplenomegaly. Haplotype analysis indicated that the families were related. (less)
|
|
Likely pathogenic
(Apr 01, 2023)
|
no assertion criteria provided
Method: clinical testing
|
Joubert syndrome 9
Affected status: yes
Allele origin:
germline
|
Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)
Accession: SCV003927889.1
First in ClinVar: Sep 16, 2023 Last updated: Sep 16, 2023 |
|
|
Pathogenic
(Aug 25, 2019)
|
no assertion criteria provided
Method: clinical testing
|
Joubert syndrome 9
Affected status: yes
Allele origin:
germline
|
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City
Accession: SCV001132927.1
First in ClinVar: Jan 06, 2020 Last updated: Jan 06, 2020 |
|
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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Expanding the phenome and variome of skeletal dysplasia. | Maddirevula S | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 29620724 |
Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity. | Bachmann-Gagescu R | Journal of medical genetics | 2015 | PMID: 26092869 |
CC2D2A is mutated in Joubert syndrome and interacts with the ciliopathy-associated basal body protein CEP290. | Gorden NT | American journal of human genetics | 2008 | PMID: 18950740 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CC2D2A | - | - | - | - |
Text-mined citations for rs118204051 ...
HelpRecord last updated Apr 06, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.