NM_025114.4(CEP290):c.5611_5614del (p.Gln1871fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 6, 2022
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:: RCV001230296.8

Allele description [Variation Report for NM_025114.4(CEP290):c.5611_5614del (p.Gln1871fs)]

NM_025114.4(CEP290):c.5611_5614del (p.Gln1871fs)

Gene:

CEP290:centrosomal protein 290 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

12q21.32

Genomic location:

Preferred name:

NM_025114.4(CEP290):c.5611_5614del (p.Gln1871fs)

HGVS:

NC_000012.12:g.88077320_88077323del
NG_008417.2:g.69897_69900del
NM_025114.4:c.5611_5614delMANE SELECT
NP_079390.3:p.Gln1871fs
LRG_694t1:c.5611_5614del
LRG_694:g.69897_69900del
LRG_694p1:p.Gln1871fs
NC_000012.11:g.88471094_88471097del
NC_000012.11:g.88471097_88471100del
NG_008417.1:g.69897_69900del
NM_025114.3:c.5611_5614del
NM_025114.3:c.5611_5614delCAAA

Protein change:

Q1871fs

Links:

dbSNP: rs727503853

NCBI 1000 Genomes Browser:

rs727503853

Molecular consequence:

NM_025114.4:c.5611_5614del - frameshift variant - [Sequence Ontology: SO:0001589]

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

Name:: Nephronophthisis
Synonyms:: juvenile nephronophthisis
Identifiers:: MONDO: MONDO:0019005; MedGen: C0687120; OMIM: PS256100; Human Phenotype Ontology: HP:0000090

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001402771	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 6, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17564967, 28497568, 16909394, 17345604, 20690115, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001402771

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 6, 2022)

germline

clinical testing

PubMed (6)
[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

CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders.

Brancati F, Barrano G, Silhavy JL, Marsh SE, Travaglini L, Bielas SL, Amorini M, Zablocka D, Kayserili H, Al-Gazali L, Bertini E, Boltshauser E, D'Hooghe M, Fazzi E, Fenerci EY, Hennekam RC, Kiss A, Lees MM, Marco E, Phadke SR, Rigoli L, Romano S, et al.

Am J Hum Genet. 2007 Jul;81(1):104-13. Epub 2007 May 18.

PubMed [citation]

PMID:: 17564967
PMCID:: PMC1950920

Neuropsychological phenotypes of 76 individuals with Joubert syndrome evaluated at a single center.

Summers AC, Snow J, Wiggs E, Liu AG, Toro C, Poretti A, Zein WM, Brooks BP, Parisi MA, Inati S, Doherty D, Vemulapalli M, Mullikin JC; NISC Comparative Sequencing Program, Vilboux T, Gahl WA, Gunay-Aygun M.

Am J Med Genet A. 2017 Jul;173(7):1796-1812. doi: 10.1002/ajmg.a.38272. Epub 2017 May 12.

PubMed [citation]

PMID:: 28497568
PMCID:: PMC5682233

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001402771.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 166831). This premature translational stop signal has been observed in individuals with Joubert syndrome (PMID: 17564967, 28497568). This variant is present in population databases (rs727503853, gnomAD 0.001%). This sequence change creates a premature translational stop signal (p.Gln1871Valfs*2) in the CEP290 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115).

#	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 29, 2024

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