ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4513A>G (p.Thr1505Ala) (rs80358682)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766851 SCV000571546 uncertain significance not provided 2016-08-30 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.4513A>G at the cDNA level, p.Thr1505Ala (T1505A) at the protein level, and results in the change of a Threonine to an Alanine (ACC>GCC). Using alternate nomenclature, this variant would be defined as BRCA2 4741A>G. This variant was observed in at least one individual with male breast cancer (Ding 2011). BRCA2 Thr1505Ala 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 Alanine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Thr1505Ala occurs at a position that is not conserved and is located in the RAD51 binding domain and POLH binding domain (Roy 2012, Buisson 2014). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA2 Thr1505Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000485977 SCV000602871 uncertain significance not specified 2017-03-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV000569819 SCV000665173 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000569819 SCV000903956 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-25 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113310 SCV000146436 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing

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