ClinVar

Description

The c.-11C>T variant was identified in the literature in 8/5532 proband chromosomes in individuals with breast cancer, and was absent in 148 control chromosomes evaluated (Borg_2010_20104584, Diez_2003_12955716, Fackenthal_2005_15744044). The variant is located in the 5’ untranslated region (promoter) and is not part of a splicing consensus sequence. It is possible that this variant may influence the binding of transcription factors and expression or processing of the BRCA2 mRNA transcript. The c.-11C>T variant was also identified in dbSNP (ID#:rs76874770), the BIC database (48X with unknown clinical significance), and in UMD (22X as an unclassified variant). In the UMD database, the variant was observed to co-occur with another BRCA2 pathogenic mutation (c.6159delT (p.Ala2054LeufsX16)) increasing the likelihood that this variant may not have clinical significance. The variant was listed in the 1000 Genomes Project with a frequency 0.005, and in the NHLBI Exome Sequencing Project with a frequency of 0.02 in African American alleles, increasing the likelihood that this may be a benign variant in certain populations of origin. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.