Submissions for variant NM_005732.4(RAD50):c.3879C>T (p.Ile1293=)

gnomAD frequency: 0.00293  dbSNP: rs28903094

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000212928	SCV000211611	benign	not specified	2013-10-25	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV000160911	SCV000212695	likely benign	Hereditary cancer-predisposing syndrome	2023-01-17	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae	RCV000160911	SCV000252804	benign	Hereditary cancer-predisposing syndrome	2024-01-29	criteria provided, single submitter	clinical testing
Counsyl	RCV000409247	SCV000489105	likely benign	Nijmegen breakage syndrome-like disorder	2016-08-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589524	SCV000698656	benign	not provided	2017-06-16	criteria provided, single submitter	clinical testing	Variant summary: The RAD50 c.3879C>T (p.Ile1293Ile) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 266/121258 control chromosomes (1 homozygote) at a frequency of 0.0021937, which is approximately 35 times the estimated maximal expected allele frequency of a pathogenic RAD50 variant (0.0000625), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign.
Eurofins Ntd Llc (ga)	RCV000212928	SCV000705549	benign	not specified	2017-01-19	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000589524	SCV002009646	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000212928	SCV002046828	benign	not specified	2021-04-01	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000212928	SCV002069726	benign	not specified	2021-01-05	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000409247	SCV002538520	benign	Nijmegen breakage syndrome-like disorder	2020-10-22	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV000589524	SCV004161375	likely benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	RAD50: BP4, BP7, BS2
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000212928	SCV001807995	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000589524	SCV001967506	likely benign	not provided		no assertion criteria provided	clinical testing