ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.705T>G (p.Asn235Lys) (rs587781484)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129444 SCV000184214 uncertain significance Hereditary cancer-predisposing syndrome 2016-04-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000129444 SCV000689028 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587198 SCV000695034 uncertain significance not provided 2016-04-25 criteria provided, single submitter clinical testing Variant summary: The c.705T>G variant affects a non-conserved nucleotide, resulting in amino acid change from Asn to Lys. 3/5 in-silico tools predict this variant to be benign. This variant is not found in 109122 control chromosomes. 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. One clinical lab via ClinVar classified this variant as VUS, without evidence to independently evaluate. 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 RCV000464180 SCV000549624 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-05-25 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 235 of the BRCA2 protein (p.Asn235Lys). The asparagine residue is moderately conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 141087). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The lysine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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