Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000410419 | SCV000488611 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2016-05-05 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781039 | SCV000918811 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2018-04-23 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.4570_4573delTTTC (p.Phe1524IlefsX18) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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 (eg. c.4587dupG, p.Lys1530fsX4; c.4631delA, p.Asn1544fsX24; c.4631dupA, p.Asn1544fsX4). The variant was absent in 120602 control chromosomes. c.4570_4573delTTTC has been reported in the literature in one individual affected with breast cancer (Kwong_2015). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV000781039 | SCV001198370 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-03-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 371845). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 26187060). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe1524Ilefs*18) 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). |
| Color Diagnostics, |
RCV001180643 | SCV001345611 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant deletes 4 nucleotides 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. 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. |
| KCCC/NGS Laboratory, |
RCV000410419 | SCV003932729 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-06-06 | criteria provided, single submitter | clinical testing | A known pathogenic mutation was detected in the BRCA2 gene (c.4570_4573delTTTC). This sequence change creates a premature translational stop signal (p.Phe1524Ilefs*18) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with breast cancer (PMID: 26187060). ClinVar contains an entry for this variant (Variation ID: 371845) with 4 submissions of which describer it as pathogenic. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). Therefore, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003475996 | SCV004210485 | pathogenic | Familial cancer of breast | 2022-09-29 | criteria provided, single submitter | clinical testing |