ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6304G>A (p.Val2102Ile) (rs80358869)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000564936 SCV000666080 likely benign Hereditary cancer-predisposing syndrome 2016-07-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification
Color RCV000564936 SCV000903840 likely benign Hereditary cancer-predisposing syndrome 2016-12-08 criteria provided, single submitter clinical testing
GeneDx RCV000766585 SCV000279431 uncertain significance not provided 2016-08-15 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.6304G>A at the cDNA level, p.Val2102Ile (V2102I) at the protein level, and results in the change of a Valine to an Isoleucine (GTA>ATA). Using alternate nomenclature, this variant would be defined as BRCA2 6532G>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Val2102Ile was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Valine and Isoleucine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Val2102Ile occurs at a position that is not conserved and is not located in a known functional domain (Borg 2010, UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRCA2 Val2102Ile is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000637345 SCV000758797 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-04-10 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 2102 of the BRCA2 protein (p.Val2102Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs80358869, ExAC 0.04%). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 234525). 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 isoleucine 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 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 RCV000222612 SCV000600691 uncertain significance not specified 2017-05-24 criteria provided, single submitter clinical testing

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