Submissions for variant NM_005732.4(RAD50):c.2202del (p.Pro734_Met735insTer)

dbSNP: rs786201789

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000164257	SCV000214881	pathogenic	Hereditary cancer-predisposing syndrome	2022-08-17	criteria provided, single submitter	clinical testing	The c.2202delC pathogenic mutation (also known as p.M735*), located in coding exon 13 of the RAD50 gene, results from a deletion of one nucleotide at position 2202. This changes the amino acid from a methionine to a stop codon within coding exon 13. 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.
Invitae	RCV000164257	SCV000261003	pathogenic	Hereditary cancer-predisposing syndrome	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Met735*) 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 (rs769230013, gnomAD 0.006%). 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: 184917). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV001781510	SCV002019615	pathogenic	Nijmegen breakage syndrome-like disorder	2021-03-24	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV001781510	SCV002538473	likely pathogenic	Nijmegen breakage syndrome-like disorder	2021-08-24	criteria provided, single submitter	curation
Baylor Genetics	RCV001781510	SCV004207321	likely pathogenic	Nijmegen breakage syndrome-like disorder	2023-10-15	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003477607	SCV004219304	likely pathogenic	not provided	2023-03-30	criteria provided, single submitter	clinical testing	This nonsense variant is predicted to cause the premature termination of RAD50 protein synthesis. The frequency of this variant in the general population, 0.000011 (3/276904 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. The variant has not been reported in individuals with RAD50-related conditions in the published literature. Based on the available information, this variant is classified as likely pathogenic.
PreventionGenetics, part of Exact Sciences	RCV003907517	SCV004736020	likely pathogenic	RAD50-related condition	2024-01-18	criteria provided, single submitter	clinical testing	The RAD50 c.2202delC variant is predicted to result in premature protein termination (p.Met735*). This variant was reported in individuals with breast and/or ovarian cancer (Table S7, Lilyquist et al. 2017. PubMed ID: 28888541; Table S2, Espinel et al. 2022. PubMed ID: 35626031). This variant is reported in 0.0057% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-131931494-GC-G) and is interpreted as pathogenic or likely pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/184917/). This variant is interpreted as likely pathogenic.