ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9924C>T (p.Tyr3308=) (rs4987049)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000045915 SCV000602826 benign not specified 2016-11-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV000163121 SCV000213633 likely benign Hereditary cancer-predisposing syndrome 2014-06-19 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000112823 SCV000145731 uncertain significance Breast-ovarian cancer, familial 2 1998-11-30 no assertion criteria provided clinical testing
Color RCV000163121 SCV000684101 benign Hereditary cancer-predisposing syndrome 2015-08-17 criteria provided, single submitter clinical testing
Counsyl RCV000112823 SCV000487906 likely benign Breast-ovarian cancer, familial 2 2015-12-04 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112823 SCV000578003 benign Breast-ovarian cancer, familial 2 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; http://priors.hci.utah.edu/PRIORS/) and frequency 0.0011 (African), derived from ExAC (2014-12-17).
GeneDx RCV000045915 SCV000167425 benign not specified 2014-03-14 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.
Integrated Genetics/Laboratory Corporation of America RCV000195310 SCV000494428 likely benign Hereditary breast and ovarian cancer syndrome 2015-07-09 criteria provided, single submitter clinical testing Variant Summary: The c.9924C>T variant involves the alteration of a non-conserved nucleotide resulting in a synonymous change. 5/5 in silico tools via Alamut predict no significant effect on splicing. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.008%, predominantly observed in the African subpopulation at a frequency of 0.096%. This frequency exceeds the maximal expected allele frequency for a pathogenic variant in BRCA2 (0.075%), suggesting this is a benign polymorphism found primarily in population(s) of African origin. In addition, the benign outcome of the variant is also supported by i) the variant predicted not to affect splicing and ii) in functional studies variant of interest did not differ from control cells (WT) in terms of sensitivity to MMC and etoposide, and RAD51 focus formation was robust similar to WT cells; iii) reputable databases and a diagnostic center via ClinVar classify the variant in benign spectrum. Taken together, this variant has been classified as likely benign.
Integrated Genetics/Laboratory Corporation of America RCV000590428 SCV000695282 likely benign not provided 2016-12-30 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9924C>T (p.Tyr3308Tyr) variant causes a synonymous change involving a non-conserved nucleotide, which 5/5 splice prediction tools predict no significant impact on normal splicing and no alterations to ESE binding, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 10/121266 (1/12127), predominantly in the African cohort, 10/10372 (1/1037), which does exceed the estimated maximal expected allele frequency for a pathogenic BRCA2 variant of 1/1333. Therefore, suggesting that the variant is likely a benign polymorphism found in population(s) of African origin. The variant of interest has been reported in affected individual(s) via publications although with limited additional information (ie, cosegregation and co-occurrence data). However, a functional study found the variant to not differ from control cells (WT) in terms of sensitivity to MMC and etoposide, and RAD51 focus formation. In addition, multiple clinical diagnostic laboratories cite the variant as "benign." Therefore, the variant of interest has been classified as "Likely Benign."
Invitae RCV000195310 SCV000073928 benign Hereditary breast and ovarian cancer syndrome 2017-12-16 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000590428 SCV000778726 likely benign not provided 2018-02-01 no assertion criteria provided clinical testing

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