Total submissions: 19
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000083111 | SCV000300808 | 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. |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000083111 | SCV000327114 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV000083111 | SCV000743302 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2014-10-08 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000496256 | SCV000838802 | pathogenic | Hereditary breast ovarian cancer syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000758902 | SCV000887831 | pathogenic | not provided | 2023-05-22 | criteria provided, single submitter | clinical testing | This variant causes the premature termination of BRCA2 protein synthesis. In the published literature, this variant has been reported in individuals and families with breast and/or ovarian cancer (PMIDs: 33471991 (2021), 29446198 (2018), 30287823 (2018), 25136594 (2014)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic. |
Color Diagnostics, |
RCV001175640 | SCV001339318 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 11 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 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 |
RCV000496256 | SCV001578004 | pathogenic | Hereditary breast ovarian cancer syndrome | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr1655*) 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: 17688236, 20858050, 21120943, 21709188, 23569316, 24728189, 25136594, 26681312, 29446198, 29487695). ClinVar contains an entry for this variant (Variation ID: 51750). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000758902 | SCV001789418 | pathogenic | not provided | 2022-12-21 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in individuals with BRCA2-related cancers (Sakai 2009, Caux-Moncoutier 2011); Published functional studies support a damaging effect: sensitivity to cisplatin (Sakai 2009); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed in large population cohorts (gnomAD); Also known as 5193C>A; This variant is associated with the following publications: (PMID: 25136594, 19654294, 21120943, 25525159, 29446198, 21205087, 30287823, 32377563, 33087929) |
Ambry Genetics | RCV001175640 | SCV002645762 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-02-27 | criteria provided, single submitter | clinical testing | The p.Y1655* pathogenic mutation (also known as c.4965C>A), located in coding exon 10 of the BRCA2 gene, results from a C to A substitution at nucleotide position 4965. This changes the amino acid from a tyrosine to a stop codon within coding exon 10. In one study, this variant was observed in 1/1525 unrelated patients who had BRCA1/2 genetic testing due to a personal and/or family history suspicious for Hereditary Breast and/or Ovarian Cancer (Caux-Moncoutier V et al. Hum. Mutat., 2011 Mar;32:325-34). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620) and has been reported with a carrier frequency of 0.00014 in 7051 unselected breast cancer patients and 0.00000 in 11241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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. |
Rady Children's Institute for Genomic Medicine, |
RCV004549478 | SCV004046144 | pathogenic | FLG-related disorder | criteria provided, single submitter | clinical testing | This frameshifting variant in exon 11 of 28 is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been previously reported as a heterozygous change in patients with BRCA2-related cancers (PMID: 17688236, 19654294, 20858050, 21709188, 23569316, 24728189, 25136594, 26681312, 28973083, 29371908). Loss-of-function variation in BRCA2 is an established mechanism of disease (ClinVar; HGMD Database). The c.4965C>A (p.Tyr1655Ter) variant is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.4965C>A (p.Tyr1655Ter) variant is classified as Pathogenic. | |
Ce |
RCV000758902 | SCV004132986 | pathogenic | not provided | 2023-10-01 | criteria provided, single submitter | clinical testing | BRCA2: PVS1, PM2 |
Baylor Genetics | RCV003460588 | SCV004213618 | pathogenic | Familial cancer of breast | 2023-09-02 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000496256 | SCV004848263 | pathogenic | Hereditary breast ovarian cancer syndrome | 2019-10-14 | criteria provided, single submitter | clinical testing | The p.Tyr1655X (c.4965C>A) variant in BRCA2 has been reported in at least 3 individuals with breast cancer (Caux-Moncoutier 2010, BIC database). It was absent from large population studies. This nonsense variant leads to a premature termination codon at position 1655, which is predicted to lead to a truncated or absent protein. Loss of function of the BRCA2 gene is an established disease mechanism in autosomal dominant hereditary breast and ovarian cancer syndrome (HBOC). Additionally, this variant was classified as Pathogenic on Sept 8 2016 by the ClinGen-approved ENIGMA expert panel (Variation ID: 51750). Another variant at this position, c.4965C>G, resulting in the same amino acid change, has been identified in individuals with HBOC and is classified as pathogenic by this laboratory. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HBOC. ACMG/AMP Criteria applied: PVS1, PM2, PS4_Supporting, PS1. |
Sharing Clinical Reports Project |
RCV000083111 | SCV000115185 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2012-10-12 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000083111 | SCV000146513 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2002-07-11 | no assertion criteria provided | clinical testing | |
Research Molecular Genetics Laboratory, |
RCV000496256 | SCV000587735 | pathogenic | Hereditary breast ovarian cancer syndrome | 2014-01-31 | no assertion criteria provided | research | |
Diagnostic Laboratory, |
RCV000083111 | SCV000733259 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | no assertion criteria provided | clinical testing | ||
Clinical Genetics Laboratory, |
RCV000758902 | SCV001906146 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
BRCAlab, |
RCV000083111 | SCV002588880 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2022-08-26 | no assertion criteria provided | clinical testing |