ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2927_2929del (p.Ser976del) (rs80359363)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Breast Cancer Information Core (BIC) (BRCA2) RCV000113116 SCV000146142 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
GeneDx RCV000044088 SCV000210726 uncertain significance not provided 2018-04-18 criteria provided, single submitter clinical testing This in-frame deletion of three nucleotides is denoted BRCA2 c.2927_2929delCCT at the cDNA level and p.Ser976del (S976del) at the protein level. The normal sequence, with the bases that are deleted in brackets, is ATCT[delCCT]TGAA. This variant, also published as BRCA2 3155_3157del3 using alternate nomenclature, has been observed in at least one individual with a personal history of breast and/or ovarian cancer (Beristain 2007). This variant was not observed at a significant allele frequency in large population cohorts (Lek 2016). This deletion of a single Serine residue 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 c.2927_2929delCCT to be a variant of uncertain significance.
Invitae RCV000456128 SCV000072101 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-12 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 11 of the BRCA2 mRNA (c.2927_2929delCCT). This leads to the deletion of 1 amino acid residue in the BRCA2 protein (p.Ser976del) but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs751328384, ExAC 0.009%). This variant has been reported in an individual affected with breast and/or ovarian cancer (PMID: 17262179). ClinVar also contains an entry for this variant (Variation ID: 51373). 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.

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