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Intellectual disability

Gene: CEP85L

Amber List (moderate evidence)

CEP85L (centrosomal protein 85 like)
EnsemblGeneIds (GRCh38): ENSG00000111860
EnsemblGeneIds (GRCh37): ENSG00000111860
CEP85L is in 3 panels

2 reviews

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least nine variants reported in nine unrelated families. PMID 32097630 comments that - the CEP85L gene as a whole is tolerant to loss of function and to missense variation. However, the 4 missense variants that have been identified in patients affect a 15-aa region of the protein that is highly intolerant to missense variation, the splicing and start-loss variants are predicted to produce a shortened protein that excludes the same 15-aa region. It is speculated that variants in this constrained region, may act through a dominant-negative mechanism.
Intellectual disability was apparent in eight of the families studied, ranging from mild (three families) to moderate (five families).
Supportive studies were also presented (PMID 32097630, 32097629).
Created: 20 Jul 2021, 3:23 p.m. | Last Modified: 20 Jul 2021, 3:23 p.m.
Panel Version: 3.1200
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Created: 20 Jul 2021, 2:35 p.m. | Last Modified: 20 Jul 2021, 2:35 p.m.
Panel Version: 3.1200

Rachel Challis (Cambridge University Hospitals NHS Foundation Trust)

Green List (high evidence)

Recommend adding as Green gene to GMS - R29 Intellectual disability panel.

Monoallelic missense and loss of function variants in CEP85L are associated with Lissencephaly (OMIM 618873). Over 10 unrelated families have been described with de novo and inherited rare variants in CEP85L. Functional work in cell lines and knockdown of Cep85l in mice confirms the role of CEP85L in neuronal migration.
PMID: 32097629
PMID: 32097630
Sources: NHS GMS
Created: 15 Jul 2021, 11:57 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual disability; epilepsy, lissencephaly

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
Phenotypes
  • Lissencephaly 10, OMIM:618873
  • Lissencephaly 10, MONDO:0030031
Tags
Q3_21_rating
Clinvar variants
Variants in CEP85L
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

20 Jul 2021, Gel status: 2

Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q3_21_rating tag was added to gene: CEP85L.

20 Jul 2021, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: cep85l has been classified as Amber List (Moderate Evidence).

20 Jul 2021, Gel status: 0

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: CEP85L were changed from Intellectual disability; epilepsy, lissencephaly to Lissencephaly 10, OMIM:618873; Lissencephaly 10, MONDO:0030031

15 Jul 2021, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Rachel Challis (Cambridge University Hospitals NHS Foundation Trust)

gene: CEP85L was added gene: CEP85L was added to Intellectual disability. Sources: NHS GMS Mode of inheritance for gene: CEP85L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CEP85L were set to 32097629; 32097630 Phenotypes for gene: CEP85L were set to Intellectual disability; epilepsy, lissencephaly Penetrance for gene: CEP85L were set to unknown Review for gene: CEP85L was set to GREEN gene: CEP85L was marked as current diagnostic