Submissions for variant NM_005732.4(RAD50):c.572C>T (p.Thr191Ile)

gnomAD frequency: 0.00469  dbSNP: rs2230017

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000030963	SCV000053553	benign	Hereditary cancer-predisposing syndrome	2014-07-25	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
GeneDx	RCV000195197	SCV000211602	benign	not specified	2013-12-02	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.
Genetic Services Laboratory, University of Chicago	RCV000195197	SCV000248651	likely benign	not specified	2014-12-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000030963	SCV000262184	benign	Hereditary cancer-predisposing syndrome	2025-02-03	criteria provided, single submitter	clinical testing
Counsyl	RCV000409597	SCV000489051	benign	Nijmegen breakage syndrome-like disorder	2016-08-09	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000442405	SCV000511671	likely benign	not provided	2017-01-24	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000442405	SCV000698659	benign	not provided	2016-08-29	criteria provided, single submitter	clinical testing	Variant summary: The RAD50 c.572C>T (p.Thr191Ile) variant involves the alteration of a conserved nucleotide. 3/3 in silico tools predict a damaging outcome for this variant; however they are not definitive and the predictions have yet to be confirmed by published functional studies. This variant was found in 210/119642 control chromosomes (1 homozygote), predominantly observed in the African subpopulation at a frequency of 0.0147207 (146/9918). This frequency is about 236 times the estimated maximal expected allele frequency of a pathogenic RAD50 variant (0.0000625), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. A large case-control study that used 2,984 breast cancer cases and 7,545 controls did not find an elevated risk for breast cancer due to this variant; instead, a protective effect was observed (OR: 0.44; p=0.0069) (Haiman_2013). In addition, multiple clinical diagnostic laboratories have classified this variant as benign/likely benign. Taken together, this variant is classified as Benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000195197	SCV002047249	benign	not specified	2021-06-08	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315525	SCV004017231	benign	Familial cancer of breast	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000442405	SCV005226550	likely benign	not provided		criteria provided, single submitter	not provided