ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9216G>A (p.Val3072=) (rs773533016)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481965 SCV000565757 uncertain significance not provided 2016-11-14 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9216G>A at the DNA level. Although this variant is silent at the coding level, preserving a Valine at codon 3072, it is predicted to create a cryptic splice donor site upstream of the natural splice donor site and to possibly cause abnormal splicing. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant was observed in a cohort of individuals with a personal and/or family history of breast and/or ovarian cancer (Caux-Moncoutier 2011). BRCA2 c.9216G>A was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.The nucleotide which is altered, a guanine (G) at base 9216, is not conserved. Based on currently available information, it is unclear whether BRCA2 c.9216G>A is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000691331 SCV000819107 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-04-20 criteria provided, single submitter clinical testing This sequence change affects codon 3072 of the BRCA2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the BRCA2 protein. This variant is present in population databases (rs773533016, ExAC 0.002%). This variant has been reported in at least one individual who underwent genetic screening due to a personal and/or family history of breast and/or ovarian cancer (PMID: 21120943). ClinVar contains an entry for this variant (Variation ID: 418592). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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