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NM_001378615.1(CC2D2A):c.4179+1del AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 22, 2024
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:
RCV000696362.15

Allele description [Variation Report for NM_001378615.1(CC2D2A):c.4179+1del]

NM_001378615.1(CC2D2A):c.4179+1del

Gene:
CC2D2A:coiled-coil and C2 domain containing 2A [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
4p15.32
Genomic location:
Preferred name:
NM_001378615.1(CC2D2A):c.4179+1del
HGVS:
  • NC_000004.12:g.15587930del
  • NG_013035.1:g.123065del
  • NM_001080522.2:c.4179+1del
  • NM_001378615.1:c.4179+1delMANE SELECT
  • NM_001378617.1:c.4032+1del
  • LRG_697t1:c.4179+1del
  • LRG_697:g.123065del
  • NC_000004.11:g.15589552del
  • NC_000004.11:g.15589553del
  • NM_001080522.2:c.4179+1delG
  • NM_001080522.2:c.4179delG
  • NM_001378615.1:c.4179+1del
Links:
dbSNP: rs386833760
NCBI 1000 Genomes Browser:
rs386833760
Molecular consequence:
  • NM_001080522.2:c.4179+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001378615.1:c.4179+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001378617.1:c.4032+1del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Familial aplasia of the vermis
Synonyms:
CEREBELLOPARENCHYMAL DISORDER IV; Joubert syndrome; Cerebelloparenchymal disorder 4; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0018772; MedGen: C0431399; Orphanet: 475; OMIM: PS213300
Name:
Meckel-Gruber syndrome
Synonyms:
DYSENCEPHALIA SPLANCHNOCYSTICA; Gruber syndrome; Dysencephalia splachnocystica
Identifiers:
MONDO: MONDO:0018921; MedGen: C0265215; OMIM: PS249000

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000824920Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 22, 2024) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

CC2D2A mutations in Meckel and Joubert syndromes indicate a genotype-phenotype correlation.

Mougou-Zerelli S, Thomas S, Szenker E, Audollent S, Elkhartoufi N, Babarit C, Romano S, Salomon R, Amiel J, Esculpavit C, Gonzales M, Escudier E, Leheup B, Loget P, Odent S, Roume J, Gérard M, Delezoide AL, Khung S, Patrier S, Cordier MP, Bouvier R, et al.

Hum Mutat. 2009 Nov;30(11):1574-82. doi: 10.1002/humu.21116.

PubMed [citation]
PMID:
19777577
PMCID:
PMC2783384
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000824920.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change affects a splice site in intron 33 of the CC2D2A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CC2D2A are known to be pathogenic (PMID: 19777577). This variant is present in population databases (rs386833761, gnomAD 0.09%). Disruption of this splice site has been observed in individual(s) with Joubert and/or Meckel-Gruber syndrome (PMID: 19777577, 26092869). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.4179del. ClinVar contains an entry for this variant (Variation ID: 56312). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 24, 2024