ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.3036+5G>A (rs181016343)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115952 SCV000053552 likely benign Hereditary cancer-predisposing syndrome 2017-07-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification,Subpopulation frequency in support of benign classification
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514683 SCV000610171 uncertain significance not provided 2017-09-05 criteria provided, single submitter clinical testing
Counsyl RCV000412309 SCV000489291 uncertain significance Nijmegen breakage syndrome-like disorder 2016-09-13 criteria provided, single submitter clinical testing
Department of Genetics,Sultan Qaboos University Hospital, Oman RCV000412309 SCV000891635 uncertain significance Nijmegen breakage syndrome-like disorder 2017-12-30 criteria provided, single submitter curation
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000203146 SCV000258028 uncertain significance not specified 2015-03-06 criteria provided, single submitter clinical testing
GeneDx RCV000514683 SCV000149861 uncertain significance not provided 2017-08-10 criteria provided, single submitter clinical testing RAD50 has been only recently described in association with cancer predisposition and the risks are not well understood. This variant is denoted RAD50 IVS19+5G>A, or c.3036+5G>A and consists of a G>A nucleotide substitution at the +5 position of intron 19 of the RAD50 gene. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD50 3036+5G>A occurs at a position that is well conserved throughout evolution. This particular nucleotide substitution was observed in multiple subpopulations, with the highest allele frequency of 0.09% (8/8588) in European Americans in the NHLBI Exome Sequencing Project. Multiple in silico splicing models predict a reduced likelihood that the nearby canonical donor splice site is utilized. At the molecular level, the impact of this missense variant on protein structure and function is not known and we consider this to be a variant of uncertain significance. Futhermore, based on the currently available information, cancer risks associated with this variant, and the RAD50 gene, remain unclear.
GeneKor MSA RCV000115952 SCV000822153 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000203146 SCV000596682 uncertain significance not specified 2016-06-24 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000203146 SCV000918115 likely benign not specified 2017-11-20 criteria provided, single submitter clinical testing Variant summary: The RAD50 c.3036+5G>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict a weakening effect on the canonical splicing donor site and 3/5 predict loss of a cryptic splicing donor site at the nucleotide of interest. However, these predictions have yet to be confirmed by functional studies. This variant was found in 352/276630 control chromosomes, predominantly observed in the Ashkenazi Jewish subpopulation at a frequency of 0.013132 (133/10128). This frequency is about 210 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 Ashkenazi Jewish origin. This variant has been reported in affected individuals without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/VUS, all without evidence for independent evaluation. Taken together, this variant is currently classified as likely benign.
Invitae RCV000115952 SCV000253464 benign Hereditary cancer-predisposing syndrome 2018-01-07 criteria provided, single submitter clinical testing
Vantari Genetics RCV000115952 SCV000267085 uncertain significance Hereditary cancer-predisposing syndrome 2016-01-06 criteria provided, single submitter clinical testing

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