ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6778_6779delinsTT (p.Glu2260Leu)

dbSNP: rs2072565206
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001245699 SCV001419002 uncertain significance Hereditary breast ovarian cancer syndrome 2025-01-15 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with leucine, which is neutral and non-polar, at codon 2260 of the BRCA2 protein (p.Glu2260Leu). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 970176). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV003158616 SCV003847547 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Ambry Genetics RCV003158616 SCV005548688 uncertain significance Hereditary cancer-predisposing syndrome 2024-08-08 criteria provided, single submitter clinical testing The c.6778_6779delGAinsTT variant (also known as p.E2260L), located in coding exon 10 of the BRCA2 gene, results from an in-frame deletion of GA and insertion of TT at nucleotide positions 6778 to 6779. This results in the substitution of the glutamic acid residue for a leucine residue at codon 2260, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the available evidence, the clinical significance of this variant remains unclear.

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