ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6458C>T (p.Pro2153Leu) (rs276174873)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131036 SCV000185966 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes)
Breast Cancer Information Core (BIC) (BRCA2) RCV000113594 SCV000146862 not provided Breast-ovarian cancer, familial 2 no assertion provided clinical testing
Color RCV000131036 SCV000903445 likely benign Hereditary cancer-predisposing syndrome 2015-11-30 criteria provided, single submitter clinical testing
GeneDx RCV000218559 SCV000278869 uncertain significance not provided 2016-02-19 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.6458C>T at the cDNA level, p.Pro2153Leu (P2153L) at the protein level, and results in the change of a Proline to a Leucine (CCA>CTA). Using alternate nomenclature, this variant would be defined as BRCA2 6686C>T. This variant has not, to our knowledge, been published in the literature as pathogenic germline variant or benign polymorphism. However, it has been reported as a somatic variant in cutaneous squamous cell carcinoma (Li 2015). BRCA2 Pro2153Leu 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 Proline and Leucine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Pro2153Leu occurs at a position that is not conserved and is not located in a known functional domain (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 Pro2153Leu is pathogenic or benign. We consider it to be a variant of uncertain significance.

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