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Intellectual disability

Gene: CDH15

Red List (low evidence)
CDH15 (cadherin 15)
EnsemblGeneIds (GRCh38): ENSG00000129910
EnsemblGeneIds (GRCh37): ENSG00000129910
OMIM: 114019, Gene2Phenotype
CDH15 is in 2 panels

7 reviews

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 14 Mar 2022, 2:22 p.m. | Last Modified: 14 Mar 2022, 2:22 p.m.
Panel Version: 3.1519
Created: 14 Mar 2022, 2:22 p.m.
Last Modified: 14 Mar 2022, 2:22 p.m.
Panel version: 3.1519

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Gene should be demoted to Red as there is limited evidence supporting this gene-disease association. The only cases reported to date with SNVs were discovered by targeted sequencing of CDH15. Clinical information was limited, describing only mild ID in some cases. There are also multiple benign LOF variants in population databases. Asymptomatic carriers lead authors to suggest incomplete penetrance but all identified variants are in gnomAD so are unlikely to be causal.
Created: 25 Oct 2021, 10:50 a.m. | Last Modified: 25 Oct 2021, 10:50 a.m.
Panel Version: 3.1381
Created: 25 Oct 2021, 10:50 a.m.
Last Modified: 25 Oct 2021, 10:50 a.m.
Panel version: 3.1381

Zornitza Stark (Australian Genomics)

Red List (low evidence)

PMID: 19012874 - 4 unrelated patients with missense variants and mild-severe ID. Only two genes checked. All variants are common in gnomAD (>20 hets each) and classified as VUS or likely benign in ClinVar (paper is from 2008, pre-dates gnomAD). Functional studies were performed showing a LOF effect, where cell adhesion was reduced.
However NMD PTCs are present in gnomAD (many >=6 hets each)

PMID: 12052883 - null mouse model were viable, showed no gross developmental defects. In particular, the skeletal musculature appeared essentially normal. In the cerebellum of M-cadherin-lacking mutants, typical contactus adherens junctions were present and similar in size and numbers to the equivalent junctions in wild-type animals. However, the adhesion plaques in the cerebellum of these mutants appeared to contain elevated levels of N-cadherin compared to wild-type animals.

PMID: 28422132 - reviewed microdeletions spanning multiple genes including CDH15, suggests it may contribute to a more severe neurological phenotype, with particular regard to brain malformations.

PMID: 26506440 - speculates low penetrance for PTCs in this gene. Acknowledges variants in ExAC, describes them as benign

Note no P/LP variants in ClinVar
Created: 30 Sep 2021, 1:59 a.m. | Last Modified: 30 Sep 2021, 1:59 a.m.
Panel Version: 3.1313

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Mental retardation, autosomal dominant 3, MIM#612580

Publications

Created: 30 Sep 2021, 1:59 a.m.
Last Modified: 30 Sep 2021, 1:59 a.m.
Panel version: 3.1313

Caroline Wright (Sanger)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
MENTAL RETARDATION AUTOSOMAL DOMINANT TYPE 3 (MRD3)

Publications

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_gilissen_2014_known . Main mutation mechanism : Loss of function
Created: 27 Jul 2017, 5:17 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; find_uk10k; gilissen_2014_known; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; GEL_ID_green_20160217; neuro_20160418_strict; Loss of function. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 12:09 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

Created: 2 Aug 2017, 3:36 p.m.

Panel version: 1.354

Dominic McMullan (Birmingham Women's NHS Foundation Trust)

Red List (low evidence)

Evidence limited largely to single paper Bahalla (2008) and not yet recapitulated via exome seq analysis; which would be expected. In addition LOF variants are reported scattered throughout the gene in ExAC

Created: 29 Apr 2016, 1:57 p.m.

Mode of inheritance
Unknown

Publications

Mode of pathogenicity
Other

Created: 29 Apr 2016, 1:57 p.m.

Panel version: 1.1

Lu Raymond (university of cambridge )

Green List (high evidence)

Created: 23 Feb 2016, 10:44 a.m.

Panel version: 0.306

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Victorian Clinical Genetics Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Mental retardation, autosomal dominant 3, OMIM:612580
OMIM
114019
Clinvar variants
Variants in CDH15
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

14 Mar 2022, Gel status: 1

Removed Tag

Ivone Leong (Genomics England Curator)

Tag watchlist was removed from gene: CDH15.

14 Mar 2022, Gel status: 1

Removed Tag, Added Tag

Ivone Leong (Genomics England Curator)

Tag Q4_21_rating was removed from gene: CDH15. Tag watchlist tag was added to gene: CDH15.

14 Mar 2022, Gel status: 1

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source Expert Review Red was added to CDH15. Rating Changed from Green List (high evidence) to Red List (low evidence)

25 Oct 2021, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q4_21_rating tag was added to gene: CDH15.

25 Oct 2021, Gel status: 3

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: cdh15 has been classified as Green List (High Evidence).

25 Oct 2021, Gel status: 3

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: CDH15 were set to

25 Oct 2021, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: CDH15 were changed from Mental retardation, autosomal dominant 3, 612580; MENTAL RETARDATION AUTOSOMAL DOMINANT TYPE 3 (MRD3) to Mental retardation, autosomal dominant 3, OMIM:612580

28 Sep 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to CDH15.

12 Mar 2018, Gel status: 3

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 1

Set Mode of Inheritance, Added New Source

Ellen McDonagh (Genomics England Curator)

CDH15 was added to Intellectual disabilitypanel. Source: Expert Review Green Model of inheritance for gene CDH15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

CDH15 was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen