ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.3165-4A>T (rs104895050)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129117 SCV000183832 benign Hereditary cancer-predisposing syndrome 2015-11-05 criteria provided, single submitter clinical testing In silico models in agreement (benign);General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
GeneDx RCV000212923 SCV000211608 benign not specified 2013-12-26 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.
Invitae RCV000129117 SCV000252802 benign Hereditary cancer-predisposing syndrome 2019-12-31 criteria provided, single submitter clinical testing
Counsyl RCV000410040 SCV000489664 benign Nijmegen breakage syndrome-like disorder 2016-11-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000212923 SCV001338166 benign not specified 2020-02-17 criteria provided, single submitter clinical testing Variant summary: RAD50 c.3165-4A>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 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 0.0033 in 250358 control chromosomes in the gnomAD database, including 10 homozygotes. The observed variant frequency is approximately 53 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 benign. To our knowledge, no occurrence of c.3165-4A>T in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have 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. Based on the evidence outlined above, the variant was classified as benign.
Harris Lab, University of Minnesota RCV000114869 SCV000148764 not provided not provided no assertion provided not provided

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