Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000661493 | SCV000783778 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2017-12-15 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
| Ambry Genetics | RCV000509826 | SCV000608236 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-10-31 | criteria provided, single submitter | clinical testing | The p.E1146* pathogenic mutation (also known as c.3436G>T), located in coding exon 10 of the BRCA2 gene, results from a G to T substitution at nucleotide position 3436. This changes the amino acid from a glutamic acid to a stop codon within coding exon 10. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Color Diagnostics, |
RCV000509826 | SCV000912368 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-05-19 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 11 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251006 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780006 | SCV000916996 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2017-12-15 | criteria provided, single submitter | clinical testing | Variant summary: The BRCA2 c.3436G>T (p.Glu1146X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., p.Phe1182fsX1 and p.Lys1191fsX6). One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/245794 control chromosomes at a frequency of 0.0000041, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). One clinical diagnostic laboratory classified this variant as pathogenic. The variant of interest has not, to our knowledge, been reported in affected individuals via publications, nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic. |
| Labcorp Genetics |
RCV000780006 | SCV001234951 | pathogenic | Hereditary breast ovarian cancer syndrome | 2024-11-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu1146*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 441504). For these reasons, this variant has been classified as Pathogenic. |