Submissions for variant NM_000059.4(BRCA2):c.5914G>C (p.Ala1972Pro)

dbSNP: rs1064795405

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000479769	SCV000571172	uncertain significance	not provided	2016-08-01	criteria provided, single submitter	clinical testing	This variant is denoted BRCA2 c.5914G>C at the cDNA level, p.Ala1972Pro (A1972P) at the protein level, and results in the change of an Alanine to a Proline (GCA>CCA). Using alternate nomenclature, this variant would be defined as BRCA2 6142G>C. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Ala1972Pro 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 Alanine and Proline differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Ala1972Pro occurs at a position that is not conserved and is located in the RAD51 binding domain (Roy 2012). 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 Ala1972Pro is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
University of Washington Department of Laboratory Medicine, University of Washington	RCV003157586	SCV003850775	likely benign	Hereditary cancer-predisposing syndrome	2023-03-23	criteria provided, single submitter	curation	Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).