ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4141_4143del (p.Lys1381del) (rs587782157)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130747 SCV000185638 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000160284 SCV000210744 uncertain significance not provided 2018-09-28 criteria provided, single submitter clinical testing This in-frame deletion of three nucleotides in BRCA2 is denoted c.4141_4143delAAA at the cDNA level and p.Lys1381del (K1381del) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 4669_4671delAAA. The normal sequence, with the bases that are deleted in brackets, is GATT[delAAA]GAAG. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Lys1381del was not observed in large population cohorts (Lek 2016). This deletion of a single Lysine amino acid 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 Lys1381del to be a variant of uncertain significance.
Invitae RCV000553746 SCV000635342 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-22 criteria provided, single submitter clinical testing This variant, c.4141_4143delAAA, results in the deletion of 1 amino acid(s) of the BRCA2 protein (p.Lys1381del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 141985). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid 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.

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.