ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.3153G>A (p.Leu1051=) (rs35800931)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162640 SCV000213077 likely benign Hereditary cancer-predisposing syndrome 2014-05-29 criteria provided, single submitter clinical testing
Counsyl RCV000409828 SCV000489114 benign Nijmegen breakage syndrome-like disorder 2016-08-22 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000194174 SCV000248650 likely benign not specified 2015-04-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000194174 SCV000920112 benign not specified 2018-05-18 criteria provided, single submitter clinical testing Variant summary: RAD50 c.3153G>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.001 in 276550 control chromosomes, predominantly at a frequency of 0.011 within the African subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 175.99 fold of the estimated maximal expected allele frequency for a pathogenic variant in RAD50 causing Hereditary Breast and Ovarian Cancer phenotype (6.3e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. Co-occurrences with other potentially pathogenic variant(s) have been reported (RAD50 c.552-1G>A), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000162640 SCV000262213 benign Hereditary cancer-predisposing syndrome 2018-01-10 criteria provided, single submitter clinical testing

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