Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000540222 | SCV000635670 | pathogenic | Hereditary breast ovarian cancer syndrome | 2024-09-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu2850*) 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: 462483). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV000571409 | SCV000666101 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-02-21 | criteria provided, single submitter | clinical testing | The p.E2850* pathogenic mutation (also known as c.8548G>T), located in coding exon 19 of the BRCA2 gene, results from a G to T substitution at nucleotide position 8548. This changes the amino acid from a glutamic acid to a stop codon within coding exon 19. 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, |
RCV000571409 | SCV001346694 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-03-02 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 20 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 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000540222 | SCV002766578 | pathogenic | Hereditary breast ovarian cancer syndrome | 2022-11-21 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.8548G>T (p.Glu2850X) 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. The variant was absent in 251214 control chromosomes. To our knowledge, no occurrence of c.8548G>T in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Institute for Biomarker Research, |
RCV000540222 | SCV005415583 | pathogenic | Hereditary breast ovarian cancer syndrome | 2024-10-01 | criteria provided, single submitter | clinical testing | The stop gained NM_000059.4(BRCA2):c.8548G>T (p.Glu2850Ter) has been reported to ClinVar as Pathogenic with a status of (2 stars) criteria provided, multiple submitters, no conflicts (Variation ID 462483 as of 2024-09-05). The p.Glu2850Ter variant is novel (not in any individuals) in gnomAD. The p.Glu2850Ter variant is novel (not in any individuals) in 1kG. This variant is predicted to cause loss of normal protein function through protein truncation. The p.Glu2850Ter variant is a loss of function variant in the gene BRCA2, which is intolerant of Loss of Function variants, as indicated by the presence of existing pathogenic loss of function variant NP_000050.3:p.M1Lfs*44 and 4531 others. For these reasons, this variant has been classified as Pathogenic |