ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.767C>T (p.Thr256Ile) (rs1064794265)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000509824 SCV000607838 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000766910 SCV000568542 uncertain significance not provided 2016-06-24 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.767C>T at the cDNA level, p.Thr256Ile (T256I) at the protein level, and results in the change of a Threonine to an Isoleucine (ACA>ATA). Using alternate nomenclature, this variant would be defined as BRCA2 995C>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Thr256Ile was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Threonine and Isoleucine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Thr256Ile occurs at a position that is not conserved and is not located in a known functional domain (Roy 2012). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA2 Thr256Ile is pathogenic or benign. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000481694 SCV000600765 uncertain significance not specified 2017-06-02 criteria provided, single submitter clinical testing

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