ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3116_3118CTA[1] (p.Thr1040del) (rs1064795908)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486775 SCV000572153 uncertain significance not provided 2016-10-27 criteria provided, single submitter clinical testing This in-frame deletion of 3 nucleotides in BRCA2 is denoted c.3119_3121delCTA at the cDNA level and p.Thr1040del (T1040del) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 3347_3349delCTA. The normal sequence, with the bases that are deleted in braces, is CCTA[CTA]GTTT. This deletion of a single Threonine residue occurs at a position that is not conserved and is located in the RAD51 binding domain (Roy 2012). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Thr1040del was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since in-frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time. We consider BRCA2 Thr1040del to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000780039 SCV000917054 uncertain significance not specified 2018-11-26 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3119_3121delCTA (p.Thr1040del) results in an in-frame deletion that is predicted to remove a Thr amino acid from the encoded protein. The variant was absent in 274500 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3119_3121delCTA in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000637391 SCV000758847 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-01-09 criteria provided, single submitter clinical testing This variant, c.3119_3121delCTA, results in the deletion of 1 amino acid of the BRCA2 protein (p.Thr1040del), 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: 422639). 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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