ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.383A>G (p.Asp128Gly) (rs80358627)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044279 SCV000072292 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-06-21 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 128 of the BRCA2 protein (p.Asp128Gly). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with male breast cancer (PMID: 10690392) and a family affected with familial colorectal cancer type X (PMID: 24814045). ClinVar contains an entry for this variant (Variation ID: 51538). 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. 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.
Ambry Genetics RCV000131922 SCV000186977 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Integrated Genetics/Laboratory Corporation of America RCV000586960 SCV000694719 uncertain significance not provided 2016-12-16 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.383A>G (p.Asp128Gly) variant involves the alteration of a non-conserved nucleotide that 3/5 in silico tools predict a benign outcome, although these predictions have yet to be functionally assessed. The variant of interest was not found in controls (ExAC, 1000 Gs, or ESP). Multiple publications cite the variant in affected indivdiuals, however, with limited information (ie, lack of cosegregation and/or co-occurrence information). Multiple clinical diagnostic laboratories/databases cite the variant as "uncertain significance." Therefore, the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)."
Mendelics RCV000044279 SCV000838730 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586960 SCV000887799 uncertain significance not provided 2018-04-25 criteria provided, single submitter clinical testing
Color RCV000131922 SCV000911861 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-27 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113501 SCV000146725 uncertain significance Breast-ovarian cancer, familial 2 1999-01-15 no assertion criteria provided clinical testing

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