ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.3165-8T>G (rs369581851)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000196572 SCV000252803 benign Hereditary cancer-predisposing syndrome 2019-12-31 criteria provided, single submitter clinical testing
Counsyl RCV000663153 SCV000786308 likely benign Nijmegen breakage syndrome-like disorder 2018-04-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001194192 SCV001363537 benign not specified 2019-03-08 criteria provided, single submitter clinical testing Variant summary: RAD50 c.3165-8T>G 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. 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 0.00056 in 276852 control chromosomes (gnomAD). The observed variant frequency is approximately 9 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.3165-8T>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two 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.

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