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Skeletal dysplasia

Gene: RAD21

Amber List (moderate evidence)

RAD21 (RAD21 cohesin complex component)
EnsemblGeneIds (GRCh38): ENSG00000164754
EnsemblGeneIds (GRCh37): ENSG00000164754
OMIM: 606462, Gene2Phenotype
RAD21 is in 12 panels

4 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

Limb hypoplasia-reduction defects gp of SD- >3 cases; Review on behalf of Tracy Lester
Created: 6 Mar 2019, 11:44 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cornelia de Lange syndrome 4 614701

Eleanor Williams (Genomics England Curator)

I don't know

Comment on list classification: Promoted from red to amber. 2 cases reported in OMIM with SNV and short stature (1 case) and limb defects.
Created: 20 Nov 2019, 2:23 p.m. | Last Modified: 21 Nov 2019, 11:57 p.m.
Panel Version: 1.244
Associated with Cornelia de Lange syndrome 4 614701 in OMIM. Clinical features listed include short stature and limb defects.

OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short fingers (1 patient) and thin fingers (1 patient) and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21, aswell as other genes, were reported.

Other publications with patients with Cornelia de Lange and RAD21 variants but no major skeletal phenotype:

PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay.

PMID: 24378232 - Minor et al., 2014 - 2 patients with atypic Cornelia de Lange. Patient 1 - in frame deletion of exon 13 - presented with developmental delay, hypospadias, inguinal hernia and dysmorphic features, mild 5th finger clinodactyly. This deletion was found to be inherited from the mother who had a history of melanoma and other unspecified medical problems.
Patient 2 - c.592_593dup frameshift mutation - presented with developmental delay, characteristic facial features, hirsutism, and hand and feet anomalies (clinodactyly, syndactyly). The mother had the same frameshift mutation showing incomplete penetrance.

PMID: 27882533 - Boyle et al., 2017 - patient with microcephaly and classical CdLS facial features with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance.

PMID: 27620904 - Martinez et al., 2017 - 92 patients recruited with syndromic intellectual disability. 1 patient identified with a variant in RAD21. A diagnosis of CdLS was made.
Created: 7 May 2019, 7:29 p.m. | Last Modified: 21 Nov 2019, 11:55 p.m.
Panel Version: 1.244
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: RAD21; Initial rating suggestion: green
Created: 6 Mar 2019, 11:36 a.m.

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Associated with phenotype in OMIM and G2P. At least two variants reported
Created: 29 Jul 2016, 1:49 p.m.

Ana Beleza (Bristol Regional Genetics Service)

Green List (high evidence)

Tier 3
Created: 17 Jun 2016, 8:07 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cornelia de Lange syndrome 4 614701

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
  • NHS GMS
  • Radboud University Medical Center, Nijmegen
  • Expert list
  • Emory Genetics Laboratory
Phenotypes
  • Cornelia de Lange syndrome 4 614701
OMIM
606462
Clinvar variants
Variants in RAD21
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

20 Nov 2019, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: rad21 has been classified as Amber List (Moderate Evidence).

7 May 2019, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: RAD21 were set to

6 May 2019, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Added phenotypes Cornelia de Lange syndrome 4 614701 for gene: RAD21

6 Mar 2019, Gel status: 1

Added New Source

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to RAD21.

9 Aug 2016, Gel status: 1

panel promoted to version 1

Sarah Leigh (Genomics England Curator)

Promoted to version 1 9th August 2016

29 Jul 2016, Gel status: 1

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

29 Jul 2016, Gel status: 1

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for RAD21 were set to Cornelia de Lange syndrome 4 614701

29 Jul 2016, Gel status: 1

Set Mode of Inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for RAD21 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

29 Jul 2016, Gel status: 1

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

29 Jul 2016, Gel status: 2

Upload gene information

Sarah Leigh (Genomics England Curator)

RAD21 was added to Unexplained skeletal dysplasiapanel. Sources: Expert list,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen

18 May 2016, Gel status: 0

Added New Source

Sarah Leigh (Genomics England Curator)

RAD21 was added to Unexplained skeletal dysplasiapanel. Sources:

18 May 2016, Gel status: 0

Created

Sarah Leigh (Genomics England Curator)

RAD21 was created by sleigh