ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9116C>G (p.Pro3039Arg) (rs80359167)

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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 RCV000130896 SCV000185805 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-21 criteria provided, single submitter clinical testing In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Insufficient or conflicting evidence
GeneDx RCV000213291 SCV000279978 uncertain significance not provided 2016-03-09 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9116C>G at the cDNA level, p.Pro3039Arg (P3039R) at the protein level, and results in the change of a Proline to an Arginine (CCG>CGG). Using alternate nomenclature, this variant would be defined as BRCA2 9344C>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Pro3039Arg was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Proline and Arginine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Pro3039Arg occurs at a position that is not conserved and is located within the DNA binding domain (Yang 2002). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA2 Pro3039Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000130896 SCV000684026 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-11 criteria provided, single submitter clinical testing
Invitae RCV000707640 SCV000836742 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-29 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 3039 of the BRCA2 protein (p.Pro3039Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine. This variant is present in population databases (rs80359167, ExAC 0.002%). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 38213). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000213291 SCV001133966 uncertain significance not provided 2019-07-31 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031796 SCV000054404 uncertain significance Breast-ovarian cancer, familial 2 2006-03-15 no assertion criteria provided clinical testing

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