Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000031346 | SCV000300469 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2016-09-08 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
| Ambry Genetics | RCV000510116 | SCV000608143 | pathogenic | Hereditary cancer-predisposing syndrome | 2015-10-01 | criteria provided, single submitter | clinical testing | The p.S617* pathogenic mutation (also known as c.1850C>A or 2078C>A), located in coding exon 9 of the BRCA2 gene, results from a C to A substitution at nucleotide position 1850. This changes the amino acid from a serine to a stop codon within coding exon 9. Since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587137 | SCV000694579 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2017-03-02 | criteria provided, single submitter | clinical testing | Variant summary: The BRCA2 c.1850C>A (p.Ser617X) 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. c.1855C>T (p.Gln619X), c.1888dupA (p.Thr630fsX6), c.1889delC (p.Thr630fsX14), and c.1929delG (p.Arg645fsX15)). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 117182 control chromosomes. In addition, multiple reputable databases 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. |
| Color Diagnostics, |
RCV000510116 | SCV001353289 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-08-24 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 10 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in families affected with hereditary breast and/or ovarian cancer (Color internal data). 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. |
| Labcorp Genetics |
RCV000587137 | SCV001586126 | pathogenic | Hereditary breast ovarian cancer syndrome | 2022-01-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser617*) 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 premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 29446198). ClinVar contains an entry for this variant (Variation ID: 37765). For these reasons, this variant has been classified as Pathogenic. |
| Sharing Clinical Reports Project |
RCV000031346 | SCV000053951 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2011-07-13 | no assertion criteria provided | clinical testing |