ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2332G>A (p.Val778Ile) (rs587779360)

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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 RCV000129872 SCV000184689 likely benign Hereditary cancer-predisposing syndrome 2016-09-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Insufficient or conflicting evidence,Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
Counsyl RCV000077276 SCV000785145 uncertain significance Breast-ovarian cancer, familial 2 2017-05-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587254 SCV000694602 uncertain significance not provided 2016-06-10 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.2332G>A (p.Val778Ile) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 121066 control chromosomes. Multiple clinical diagnostic laboratories/reputable databases classified this variant as VUS / Likely Benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000230477 SCV000283187 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-30 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 778 of the BRCA2 protein (p.Val778Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. 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: 89044). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000077276 SCV000296493 uncertain significance Breast-ovarian cancer, familial 2 2016-06-08 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077276 SCV000109073 uncertain significance Breast-ovarian cancer, familial 2 2011-11-16 no assertion criteria provided clinical testing

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