ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6399_6401del (p.Asn2135del) (rs80359581)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130365 SCV000185217 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000031624 SCV000146840 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000130365 SCV000910842 likely benign Hereditary cancer-predisposing syndrome 2015-09-22 criteria provided, single submitter clinical testing
Counsyl RCV000031624 SCV000488112 uncertain significance Breast-ovarian cancer, familial 2 2015-12-28 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000031624 SCV000744490 uncertain significance Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000031624 SCV000733281 uncertain significance Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
GeneDx RCV000221731 SCV000278868 uncertain significance not provided 2018-05-16 criteria provided, single submitter clinical testing This in-frame deletion of three nucleotides in BRCA2 is denoted c.6399_6401delAAA at the cDNA level and p.Asn2135del (N2135del) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 6627_6629delAAA. The normal sequence, with the bases that are deleted in brackets, is TATC[delAAA]TAAC. This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. This variant was not observed at a significant allele frequency in large population cohorts (Lek 2016). This deletion of a single Asparagine amino acid is not located in a known functional domain. 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 Asn2135del to be a variant of uncertain significance.
Invitae RCV000197527 SCV000255254 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-06 criteria provided, single submitter clinical testing This variant, c.6399_6401delAAA, results in the deletion of 1 amino acid of the BRCA2 protein (p.Asn2135del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs80359581, ExAC 0.003%). This variant has been reported in individuals in the Breast Cancer Information Core database (PMID: 10923033) and the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 38042). 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.
Sharing Clinical Reports Project (SCRP) RCV000031624 SCV000054231 likely benign Breast-ovarian cancer, familial 2 2012-06-14 no assertion criteria provided clinical testing

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