ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8332-2A>G (rs587782774)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132304 SCV000187389 likely pathogenic Hereditary cancer-predisposing syndrome 2016-05-11 criteria provided, single submitter clinical testing The c.8332-2A>G intronic variant results from an A to G substitution two nucleotides upstream from coding exon 18 in the BRCA2 gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 225000 alleles tested) in our clinical cohort. This nucleotide position is highly conserved on sequence alignment. 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 acceptor site are typically deleterious in nature (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008; 10:294). As such, the c.8332-2A>G variant is classified as likely pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000258406 SCV000327874 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000258406 SCV000677762 likely pathogenic Breast-ovarian cancer, familial 2 2017-02-14 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353698 SCV000592183 pathogenic Malignant tumor of breast no assertion criteria provided clinical testing The c.8332-2A>G variant has not been previously identified in the literature nor by our laboratory and is of the type which is expected to cause the disorder. The c.8332-2A>G variant is located in the 3' splice region, and is predicted to cause abnormal splicing because the nucleotide substitution occurs in the invariant -1 and -2 positions of the splice consensus sequence. In summary, based on the information above this variant is Pathogenic.
Hereditary Cancer Genetics group,Vall d'Hebron Institute of Oncology RCV000503891 SCV000916371 pathogenic Hereditary breast and ovarian cancer syndrome 2019-03-01 no assertion criteria provided research

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