ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2441C>T (p.Pro814Leu) (rs80358510)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Breast Cancer Information Core (BIC) (BRCA2) RCV000113044 SCV000146049 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
GeneDx RCV000484505 SCV000567103 uncertain significance not provided 2015-07-09 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.2441C>T at the cDNA level, p.Pro814Leu (P814L) at the protein level, and results in the change of a Proline to a Leucine (CCC>CTC). Using alternate nomenclature, this variant would be defined as BRCA2 2669C>T. This variant has not, to our knowledge, been published in the literature as either a germline pathogenic variant or a benign polymorphism. However, this variant has been reported as a somatic variant in a cutaneous squamous cell carcinoma (Pickering 2014). BRCA2 Pro814Leu 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 Proline and Leucine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Pro814Leu occurs at a position that is not conserved and is within the region of interaction with NPM1 (Uniprot). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether BRCA2 Pro814Leu is pathogenic or benign. We consider it to be a variant of uncertain significance.

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