ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.67+4T>C

gnomAD frequency: 0.00001  dbSNP: rs373546450
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130680 SCV000185567 likely benign Hereditary cancer-predisposing syndrome 2019-10-15 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Michigan Medical Genetics Laboratories, University of Michigan RCV000031643 SCV000267725 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2016-04-21 criteria provided, single submitter clinical testing
Invitae RCV000228347 SCV000283298 uncertain significance Hereditary breast ovarian cancer syndrome 2024-01-18 criteria provided, single submitter clinical testing This sequence change falls in intron 2 of the BRCA2 gene. It does not directly change the encoded amino acid sequence of the BRCA2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs373546450, gnomAD 0.0009%). This variant has been observed in individual(s) with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 38061). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health RCV000130680 SCV000688993 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-22 criteria provided, single submitter clinical testing This variant causes a T to C nucleotide substitution at the +4 position of intron 2 of the BRCA2 gene. To our knowledge, RNA studies have not been reported for this variant. This variant has been reported in an individual affected with colorectal cancer (PMID: 28135145). This variant has been identified in 1/245274 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000031643 SCV000743234 likely benign Breast-ovarian cancer, familial, susceptibility to, 2 2017-07-28 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000031643 SCV000744377 benign Breast-ovarian cancer, familial, susceptibility to, 2 2015-09-21 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000031643 SCV004822817 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-04-03 criteria provided, single submitter clinical testing This variant causes a T to C nucleotide substitution at the +4 position of intron 2 of the BRCA2 gene. To our knowledge, RNA studies have not been reported for this variant. This variant has been reported in an individual affected with colorectal cancer (PMID: 28135145). This variant has been identified in 1/245274 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Sharing Clinical Reports Project (SCRP) RCV000031643 SCV000054250 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2008-08-25 no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001723595 SCV001957282 likely benign not provided no assertion criteria provided clinical testing

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