ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3966_3968del (p.Asn1322del) (rs397507319)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166560 SCV000217362 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient evidence
Color RCV000166560 SCV000688841 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-23 criteria provided, single submitter clinical testing
Counsyl RCV000238771 SCV000488130 uncertain significance Breast-ovarian cancer, familial 2 2016-02-19 criteria provided, single submitter clinical testing
GeneDx RCV000160317 SCV000210809 uncertain significance not provided 2017-02-07 criteria provided, single submitter clinical testing This in-frame deletion of three nucleotides in BRCA2 is denoted c.3966_3968delCAA at the cDNA level and p.Asn1322del (N1322del) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 c.4194_4196delCAA. The normal sequence, with the bases that are deleted in brackets, is ATAA[delCAA]ATAT. This deletion occurs in at a residue that is not conserved and is located within the RAD51 binding domain (Roy 2012). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. 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 Asn1322del to be a variant of uncertain significance.
Invitae RCV000203852 SCV000259311 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-08 criteria provided, single submitter clinical testing This variant, c.3966_3968delCAA, results in the deletion of 1 amino acid of the BRCA2 protein (p.Asn1322del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs761018415, ExAC 0.004%). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 37868). The amino acid residue affected by this in-frame deletion belongs to the BRC repeats of the BRCA2 protein that RAD51 interacts with (PMID: 22193408). However, functional studies have not been performed on the effect of this in-frame deletion. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000238771 SCV000296563 uncertain significance Breast-ovarian cancer, familial 2 2016-03-05 criteria provided, single submitter clinical testing

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