Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002433533 | SCV002677156 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2018-11-21 | criteria provided, single submitter | clinical testing | The c.8332-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 18 of the BRCA2 gene. This alteration was identified in one family of Scottish/Northern Irish descent with early onset breast and/or ovarian cancer (Scottish/Northern Irish BRCA1/BRCA2 Consortium, Br. J. Cancer 2003 Apr; 88(8):1256-62). This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
Fulgent Genetics, |
RCV002496696 | SCV002812413 | pathogenic | Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3 | 2021-12-14 | criteria provided, single submitter | clinical testing | |
Clin |
RCV000577132 | SCV000678824 | not provided | Familial cancer of breast | no assertion provided | literature only | ||
Department of Pathology and Laboratory Medicine, |
RCV001356312 | SCV001551446 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | no assertion criteria provided | clinical testing | The BRCA2 c.8332-1G>C variant was identified in 1 of 214 proband chromosomes (frequency: 0.01) from individuals or families with breast cancer (S/N Consortium 2003). The variant was also identified in dbSNP (ID: rs397507979) as “With Pathogenic, untested allele”, ClinVar (unclassified), and ARUP Laboratories (definitely pathogenic). The variant was not identified in Clinvitae, COGR, Cosmic, LOVD 3.0, UMD-LSDB, BIC Database, or Zhejiang University databases. The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.8332-1G>C variant is predicted to cause abnormal splicing because the nucleotide substitution occurs in the invariant region of the splice consensus sequence. In addition, 4 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic. |