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Primary immunodeficiency

Gene: RAD50

Red List (low evidence)

RAD50 (RAD50 double strand break repair protein)
EnsemblGeneIds (GRCh38): ENSG00000113522
EnsemblGeneIds (GRCh37): ENSG00000113522
OMIM: 604040, Gene2Phenotype
RAD50 is in 4 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Red List (low evidence)

Comment on list classification: New gene added by Boaz Palterer. Of the three total patients reported to date with biallelic variants in this gene, only one exhibited bone marrow failure and immunodeficiency (PMID: 33378670). Therefore rating Red on this panel until further cases are reported which indicate that RAD50 variants contribute to immunodeficiency
Created: 1 Apr 2021, 3:09 p.m. | Last Modified: 1 Apr 2021, 3:09 p.m.
Panel Version: 2.407
- PMID:33378670 - single patient described with bone marrow failure, immunodeficiency and developmental defects, who was compound heterozygous for a frameshift and premature stop codon (c.2165dup; p.Glu723Glyfs∗5 - maternally inherited) and in-frame deletion (c.3109_3111del; p.Glu1035del - de novo) in the RAD50 gene.
Functional characterisation using patient-derived fibroblasts indicated defects in DNA replication, DNA repair, and DNA end resection; however, ATM-dependent DNA damage response remained intact. Studies in yeast modelling the variant corresponding to p.Glu1035del produced defects in both DNA repair and Tel1ATM-dependent signalling following thermal activation.

Of note, two other unrelated individuals have also been reported with biallelic RAD50 variants and a similar phenotype (MIM# 613078) - however, neither of these cases presented immunodeficiency (PMIDs: 19409520 and 32212377)
Created: 1 Apr 2021, 1:54 p.m. | Last Modified: 1 Apr 2021, 1:54 p.m.
Panel Version: 2.406

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nijmegen breakage syndrome-like disorder, OMIM:613078

Publications

Boaz Palterer (University of Florence)

Red List (low evidence)

Chansel-Da Cruz et al. identified a single patient with bone marrow failure, immunodeficiency and developmental defect caused by compound heterozygous mutations in RAD50. The first mutations generate a null allele, the second is hypothesized to be hypomorphic because of the loss of a single amino acid residue in the coiled-coil domain of RAD50.
Sources: Literature
Created: 24 Feb 2021, 10:16 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
bone marrow failure; immunodeficiency; developmental defect

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
Phenotypes
  • Nijmegen breakage syndrome-like disorder, OMIM:613078
  • Bone marrow failure
  • Immunodeficiency
OMIM
604040
Clinvar variants
Variants in RAD50
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

1 Apr 2021, Gel status: 1

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: RAD50 were changed from bone marrow failure; immunodeficiency; developmental defect to Nijmegen breakage syndrome-like disorder, OMIM:613078; Bone marrow failure; Immunodeficiency

1 Apr 2021, Gel status: 1

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: rad50 has been classified as Red List (Low Evidence).

24 Feb 2021, Gel status: 0

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

Boaz Palterer (University of Florence)

gene: RAD50 was added gene: RAD50 was added to Primary immunodeficiency. Sources: Literature Mode of inheritance for gene: RAD50 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RAD50 were set to 33378670 Phenotypes for gene: RAD50 were set to bone marrow failure; immunodeficiency; developmental defect Penetrance for gene: RAD50 were set to unknown Review for gene: RAD50 was set to RED