Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000481160 | SCV000565954 | uncertain significance | not provided | 2015-03-13 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.272A>G at the cDNA level, p.Tyr91Cys (Y91C) at the protein level, and results in the change of a Tyrosine to a Cysteine (TAC>TGC). Using alternate nomenclature, this variant would be defined as BRCA2 500A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Tyr91Cys 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 Tyrosine and Cysteine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Tyr91Cys occurs at a position that is moderately conserved among mammals 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 Tyr91Cys is pathogenic or benign. We consider it to be a variant of uncertain significance. |