Submissions for variant NM_000059.4(BRCA2):c.7330G>C (p.Asp2444His)

dbSNP: rs398122579

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000479939	SCV000570233	uncertain significance	not provided	2016-05-04	criteria provided, single submitter	clinical testing	This variant is denoted BRCA2 c.7330G>C at the cDNA level, p.Asp2444His (D2444H) at the protein level, and results in the change of an Aspartic Acid to a Histidine (GAT>CAT). Using alternate nomenclature, this variant would be defined as BRCA2 7558G>C. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Asp2444His 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 Aspartic Acid and Histidine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Asp2444His occurs at a position that is not conserved and is located in the within the FANCD2 binding domain (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA2 Asp2444His is pathogenic or benign. We consider it to be a variant of uncertain significance.