Submissions for variant NM_005732.4(RAD50):c.2983_2986del (p.Glu995fs)

dbSNP: rs587780154

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000115951	SCV000186628	pathogenic	Hereditary cancer-predisposing syndrome	2013-07-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000115951	SCV000216431	pathogenic	Hereditary cancer-predisposing syndrome	2022-07-06	criteria provided, single submitter	clinical testing	The c.2983_2986delGAAA pathogenic mutation, located in coding exon 19 of the RAD50 gene, results from a deletion of 4 nucleotides at nucleotide positions 2983 to 2986, causing a translational frameshift with a predicted alternate stop codon (p.E995Rfs*2). This alteration has been previously identified in a Chinese breast cancer cohort (Li JY et al. Int. J. Cancer. 2019 01;144:281-289). Of note, this alteration is also designated as c.2980_2983del in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000115951	SCV000753385	pathogenic	Hereditary cancer-predisposing syndrome	2024-11-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu995Argfs*2) in the RAD50 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAD50 are known to be pathogenic (PMID: 19409520). This variant is present in population databases (rs587782488, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. ClinVar contains an entry for this variant (Variation ID: 128015). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Sema4, Sema4	RCV001781446	SCV002538490	pathogenic	Nijmegen breakage syndrome-like disorder	2022-02-24	criteria provided, single submitter	curation
Baylor Genetics	RCV001781446	SCV004207334	pathogenic	Nijmegen breakage syndrome-like disorder	2023-09-20	criteria provided, single submitter	clinical testing
Medical Genetics Laboratory, Umraniye Training and Research Hospital, University of Health Sciences	RCV001554265	SCV001774868	pathogenic	Neoplasm of the skin	2021-08-09	no assertion criteria provided	clinical testing