ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5218_5223del (p.Leu1740_Ser1741del) (rs397507775)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044615 SCV000072628 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-29 criteria provided, single submitter clinical testing This variant, c.5218_5223delTTAAGT, results in the deletion of 2 amino acids of the BRCA2 protein (p.Leu1740_Ser1741del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs757271988, ExAC 0.02%). This variant has been reported in an individual at high risk for breast and/or ovarian cancer (PMID: 22970155), and an individual affected with breast cancer (PMID: 26187060). ClinVar contains an entry for this variant (Variation ID: 51824 ). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000129461 SCV000184231 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Counsyl RCV000113403 SCV000488017 uncertain significance Breast-ovarian cancer, familial 2 2015-12-16 criteria provided, single submitter clinical testing
GeneDx RCV000766621 SCV000564786 uncertain significance not provided 2018-12-17 criteria provided, single submitter clinical testing This in-frame deletion of six nucleotides in BRCA2 is denoted c.5218_5223delTTAAGT at the cDNA level and p.Leu1740_Ser1741del (L1740_S1741del) at the protein level. Using alternate nomenclature this variant would be defined as BRCA2 5446_5451delTTAAGT. The normal sequence, with the bases that are deleted in brackets, is TTAT[delTTAAGT]AACA. This variant has been observed in several individuals with a personal and/or family history of breast and/or ovarian cancer, all of whom were of Asian descent (Kurian 2008, Kwong 2012, Li 2017). This variant was not observed at a significant allele frequency in large population cohorts (Lek 2016). This deletion is located in the RAD51 and POLH binding domains (Roy 2012, Buisson 2014). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Since in-frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider BRCA2 Leu1740_Ser1741del to be a variant of uncertain significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000480948 SCV000591952 uncertain significance not specified criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113403 SCV000146573 uncertain significance Breast-ovarian cancer, familial 2 2013-02-20 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.