Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000239050 | SCV000783851 | 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. |
| Invitae | RCV000637453 | SCV000758913 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-11-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr1410Asnfs*4) 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 not present in population databases (gnomAD no frequency). 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: 252830). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000657268 | SCV000778999 | pathogenic | not provided | 2017-09-21 | criteria provided, single submitter | clinical testing | This duplication of one nucleotide in BRCA2 is denoted c.4228dupA at the cDNA level and p.Thr1410AsnfsX4 (T1410NfsX4) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 4456dupA or 4456insA. The normal sequence, with the base that is duplicated in brackets, is GTTA[dupA]CTGC. The duplication causes a frameshift which changes a Threonine to an Asparagine at codon 1410, and creates a premature stop codon at position 4 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic. |
| Color Diagnostics, |
RCV001804979 | SCV002052142 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-02-01 | criteria provided, single submitter | clinical testing | This variant inserts 1 nucleotide in exon 11 of the BRCA2 gene, creating a frameshift and 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 not been identified 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. |
| Ambry Genetics | RCV001804979 | SCV002632784 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-12-06 | criteria provided, single submitter | clinical testing | The c.4228dupA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a duplication of A at nucleotide position 4228, causing a translational frameshift with a predicted alternate stop codon (p.T1410Nfs*4). 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. |
| Sharing Clinical Reports Project |
RCV000239050 | SCV000297433 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2013-10-08 | no assertion criteria provided | clinical testing |