Submissions for variant NM_000059.4(BRCA2):c.10061C>T (p.Ser3354Phe)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV003736442	SCV004564490	uncertain significance	not provided	2023-03-21	criteria provided, single submitter	clinical testing	The BRCA2 c.10061C>T; p.Ser3354Phe variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Computational analyses predict that this variant is neutral (REVEL: 0.090). Due to limited information, the clinical significance of this variant is uncertain at this time.
All of Us Research Program, National Institutes of Health	RCV004005933	SCV004846260	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2023-12-18	criteria provided, single submitter	clinical testing	This missense variant replaces serine with phenylalanine at codon 3354 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.