Submissions for variant NM_005732.4(RAD50):c.1174_1177del (p.Gln392fs)

dbSNP: rs1554098250

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000567846	SCV000666999	pathogenic	Hereditary cancer-predisposing syndrome	2020-04-27	criteria provided, single submitter	clinical testing	The c.1174_1177delCAGA pathogenic mutation, located in coding exon 8 of the RAD50 gene, results from a deletion of 4 nucleotides between positions 1174 and 1177, causing a translational frameshift with a predicted alternate stop codon (p.Q392Lfs*8). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000781782	SCV000920108	likely pathogenic	Nijmegen breakage syndrome-like disorder	2018-01-19	criteria provided, single submitter	clinical testing	Variant summary: The RAD50 c.1174_1177delCAGA (p.Gln392LeufsX8) variant results in a premature termination codon, predicted to cause a truncated or absent RAD50 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant is absent in 245944 control chromosomes. In addition, one clinical diagnostic laboratory/reputable database classified this variant as pathogenic. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic.
Invitae	RCV000567846	SCV001235612	pathogenic	Hereditary cancer-predisposing syndrome	2024-01-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln392Leufs*8) 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 not present in population databases (gnomAD no frequency). 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: 482086). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV000781782	SCV002019613	pathogenic	Nijmegen breakage syndrome-like disorder	2019-01-23	criteria provided, single submitter	clinical testing