ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8699A>T (p.Asp2900Val) (rs398122712)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000077641 SCV000488315 uncertain significance Breast-ovarian cancer, familial 2 2016-02-25 criteria provided, single submitter clinical testing
Invitae RCV000534579 SCV000635682 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-04-27 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with valine at codon 2900 of the BRCA2 protein (p.Asp2900Val). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and valine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 91733). 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 disruptive, but these predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on 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.
Ambry Genetics RCV000564657 SCV000666088 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-01 criteria provided, single submitter clinical testing Insufficient evidence
Color RCV000564657 SCV000906584 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-14 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001001011 SCV001158119 uncertain significance not specified 2019-01-11 criteria provided, single submitter clinical testing The BRCA2 c.8699A>T; p.Asp2900Val variant (rs398122712), also reported as 8927A>T, has been described in an individual with colorectal cancer, but its association with disease was determined to be uncertain (Yurgelun 2017). It is reported as a variant of uncertain clinical significance in ClinVar (Variation ID: 91733), and is observed on only one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The aspartic acid at codon 2900 is highly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious. However, due to limited or absent clinical and functional data regarding this variant, its clinical significance cannot be determined with certainty. REFERENCES Yurgelun M et al. Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer. J Clin Oncol. 2017 Apr 1;35(10):1086-1095.
Sharing Clinical Reports Project (SCRP) RCV000077641 SCV000109444 uncertain significance Breast-ovarian cancer, familial 2 2012-10-23 no assertion criteria provided clinical testing
Center of Medical Genetics and Primary Health Care RCV001005030 SCV000987289 risk factor breast cancer no assertion criteria provided research

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