ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1805G>T (p.Gly602Val) (rs398122732)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000572020 SCV000665328 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000572020 SCV000688726 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-25 criteria provided, single submitter clinical testing
Counsyl RCV000077666 SCV000785851 uncertain significance Breast-ovarian cancer, familial 2 2017-12-27 criteria provided, single submitter clinical testing
GeneDx RCV000758866 SCV000567807 uncertain significance not provided 2016-10-07 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.1805G>T at the cDNA level, p.Gly602Val (G602V) at the protein level, and results in the change of a Glycine to a Valine (GGA>GTA). Using alternate nomenclature, this variant would be defined as BRCA2 2033G>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Gly602Val 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 Glycine and Valine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Gly602Val occurs at a position that is not conserved and is not located in a known functional domain. 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 Gly602Val is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000824255 SCV000965146 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-21 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 602 of the BRCA2 protein (p.Gly602Val). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 91758). Algorithms developed to predict the effect of missense changes on protein structure and function 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 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758866 SCV000887762 uncertain significance not provided 2017-10-18 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077666 SCV000109469 uncertain significance Breast-ovarian cancer, familial 2 2006-05-26 no assertion criteria provided clinical testing

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