Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV004034480 | SCV005026124 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-22 | criteria provided, single submitter | clinical testing | The p.F11C variant (also known as c.32T>G), located in coding exon 1 of the BRCA2 gene, results from a T to G substitution at nucleotide position 32. The phenylalanine at codon 11 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Department of Pathology and Laboratory Medicine, |
RCV001357257 | SCV001552676 | uncertain significance | Malignant tumor of breast | no assertion criteria provided | clinical testing | The BRCA2 p.Phe11Cys variant was not identified in the literature nor was it identified in the dbSNP, ClinVar, or LOVD 3.0 databases. The variant was identified in UMD-LSDB (classified as uncertain significance). The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). The Phe11 residue is conserved in mammals but not in more distantly related organisms and 5 out of 5 computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |