Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000111963 | SCV000299852 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-09-08 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
| Ambry Genetics | RCV000509806 | SCV000607841 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-02-07 | criteria provided, single submitter | clinical testing | The c.2915delG pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 2915, causing a translational frameshift with a predicted alternate stop codon (p.G972Dfs*28). 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. |
| Counsyl | RCV000111963 | SCV000677647 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2017-01-25 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000509806 | SCV000909328 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-05-07 | criteria provided, single submitter | clinical testing | This variant deletes 1 nucleotide in exon 10 of the BRCA1 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 BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Labcorp Genetics |
RCV001382383 | SCV001581133 | pathogenic | Hereditary breast ovarian cancer syndrome | 2022-11-01 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 21520333). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly972Aspfs*28) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). ClinVar contains an entry for this variant (Variation ID: 54716). For these reasons, this variant has been classified as Pathogenic. |
| Laboratory for Molecular Medicine, |
RCV001382383 | SCV004847895 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2019-10-14 | criteria provided, single submitter | clinical testing | The p.Gly972AspfsX28 variant in BRCA1 has not been previously reported in individuals with hereditary breast and/or ovarian cancer (HBOC) and was absent from large population studies, but has been reported in ClinVar (Variation ID: 54716). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 972 and leads to a premature termination codon 28 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the BRCA1 gene is an established disease mechanism in autosomal dominant HBOC. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant HBOC. ACMG/AMP Criteria applied: PVS1, PM2. |
| Breast Cancer Information Core |
RCV000111963 | SCV000144579 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2003-12-23 | no assertion criteria provided | clinical testing |