NM_001378615.1(CC2D2A):c.517C>T (p.Arg173Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 17, 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:: RCV001853050.4

Allele description [Variation Report for NM_001378615.1(CC2D2A):c.517C>T (p.Arg173Ter)]

NM_001378615.1(CC2D2A):c.517C>T (p.Arg173Ter)

Gene:

CC2D2A:coiled-coil and C2 domain containing 2A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p15.32

Genomic location:

Preferred name:

NM_001378615.1(CC2D2A):c.517C>T (p.Arg173Ter)

HGVS:

NC_000004.12:g.15510217C>T
NG_013035.1:g.45352C>T
NM_001080522.2:c.517C>T
NM_001378615.1:c.517C>TMANE SELECT
NM_001378617.1:c.370C>T
NP_001073991.2:p.Arg173Ter
NP_001365544.1:p.Arg173Ter
NP_001365546.1:p.Arg124Ter
LRG_697t1:c.517C>T
LRG_697:g.45352C>T
LRG_697p1:p.Arg173Ter
NC_000004.11:g.15511840C>T

Protein change:

R124*

Links:

dbSNP: rs386833763

NCBI 1000 Genomes Browser:

rs386833763

Molecular consequence:

NM_001080522.2:c.517C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001378615.1:c.517C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001378617.1:c.370C>T - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

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S41 family peptidase [Aquimarina sp. AD10]
S41 family peptidase [Aquimarina sp. AD10]
gi|1468741359|gnl|PRJNA485019|D1816 5|gb|AXT61907.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002210866	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 17, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19777577, 21866095, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002210866

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 17, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Genotype-phenotype correlation in 440 patients with NPHP-related ciliopathies.

Chaki M, Hoefele J, Allen SJ, Ramaswami G, Janssen S, Bergmann C, Heckenlively JR, Otto EA, Hildebrandt F.

Kidney Int. 2011 Dec;80(11):1239-45. doi: 10.1038/ki.2011.284. Epub 2011 Aug 24.

PubMed [citation]

PMID:: 21866095
PMCID:: PMC4037742

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002210866.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Arg173*) in the CC2D2A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CC2D2A are known to be pathogenic (PMID: 19777577). This variant is present in population databases (rs386833763, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with clinical features of Joubert syndrome and related disorders (PMID: 19777577, 21866095). ClinVar contains an entry for this variant (Variation ID: 56315). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 16, 2024

ClinVar

Relating variation to medicine