| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Severe microcephaly v2.293 | RAD50 | Eleanor Williams Tag Q2_21_rating was removed from gene: RAD50. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.292 | RAD50 | Sarah Leigh commented on gene: RAD50 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.291 | RAD50 |
Eleanor Williams Source Expert Review Green was added to RAD50. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Severe microcephaly v2.108 | RAD50 | Arina Puzriakova Phenotypes for gene: RAD50 were changed from Nijmegen breakage syndrome-like disorder, 613078 to Nijmegen breakage syndrome-like disorder, OMIM:613078 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.107 | RAD50 | Arina Puzriakova Publications for gene: RAD50 were set to 1887849; 19409520; 32212377 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.106 | RAD50 | Arina Puzriakova Classified gene: RAD50 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.106 | RAD50 | Arina Puzriakova Added comment: Comment on list classification: There are now a total of 3 unrelated cases (PMIDs: 19409520; 32212377; 33378670) with a RAD50‐related syndrome including microcephaly. This therefore reaches the threshold for promotion of this gene to Green status at the next review (removed 'watchlist' tag and added 'Q2_21_rating' tag) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.106 | RAD50 | Arina Puzriakova Gene: rad50 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.105 | RAD50 |
Arina Puzriakova Tag watchlist was removed from gene: RAD50. Tag Q2_21_rating tag was added to gene: RAD50. |
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| Severe microcephaly v2.105 | RAD50 |
Arina Puzriakova edited their review of gene: RAD50: Added comment: - PMID: 33378670 (2020) - single patient described with bone marrow failure, immunodeficiency and developmental defects (including microcephaly), 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.; Changed rating: GREEN; Changed publications: 19409520, 32212377, 33378670; Changed phenotypes: Nijmegen breakage syndrome-like disorder, OMIM:613078; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal |
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| Severe microcephaly v2.24 | RAD50 | Arina Puzriakova Tag watchlist tag was added to gene: RAD50. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.24 | RAD50 | Arina Puzriakova Phenotypes for gene: RAD50 were changed from Nijmegen breakage syndrome-like disorder, MIM# 613078 to Nijmegen breakage syndrome-like disorder, 613078 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.23 | RAD50 | Arina Puzriakova Publications for gene: RAD50 were set to 19409520; 32212377 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.22 | RAD50 | Arina Puzriakova Classified gene: RAD50 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.22 | RAD50 |
Arina Puzriakova Added comment: Comment on list classification: Relevant phenotype (two unrelated cases with severe congenital microcephaly) but additional cases required before inclusion of RAD50 on a diagnostic panel. Rating Amber in anticipation of additional publications/clinical evidence (added to watchlist). |
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| Severe microcephaly v2.22 | RAD50 | Arina Puzriakova Gene: rad50 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.21 | RAD50 |
Zornitza Stark gene: RAD50 was added gene: RAD50 was added to Severe microcephaly. Sources: Literature Mode of inheritance for gene: RAD50 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RAD50 were set to 19409520; 32212377 Phenotypes for gene: RAD50 were set to Nijmegen breakage syndrome-like disorder, MIM# 613078 Review for gene: RAD50 was set to GREEN gene: RAD50 was marked as current diagnostic Added comment: Two individuals reported with bi-allelic variants in this gene showing dysmorphic facial features similar to NBS, short stature, microcephaly, and mild/moderate intellectual disability. Fibroblasts established from one of the individuals showed chromosomal instability and abnormal radioresistant DNA synthesis. The MRE11/RAD50/NBN (MRN) complex is involved in signaling processes inducing the repair of DNA double-strand breaks. Variants in NBN and MRE11 are associated with Nijmegen breakage syndrome (NBS) and ataxia telangiectasia (AT)‐like disorder, respectively, so this gene is a strong biological candidate for this phenotype. Sources: Literature |
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