ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.291_296del (p.Glu97_Leu98del) (rs80359362)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000589249 SCV000210789 uncertain significance not provided 2014-03-07 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.291_296delATTAGA at the cDNA level and p.Glu97_Leu98del at the protein level. The normal sequence, with the bases that are deleted in brackets, is AAGA[delATTAGA]TAAA. This in frame deletion of 6 base pairs occurs in a region which is well conserved and is not located in a known functional domain. This variant has been reported one time in the Breast Cancer Information Core (BIC) database as a variant of unknown clinical importance, but 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 Glu97_Leu98del to be a variant of uncertain significance.
Invitae RCV000204993 SCV000260171 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-09-19 criteria provided, single submitter clinical testing This sequence change deletes 6 nucleotides from exon 3 of the BRCA2 mRNA (c.291_296delAGAATT). This leads to the deletion of 2 amino acid residues in the BRCA2 protein (p.Glu97_Leu98del) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual in the Breast Cancer Information Core database, co-occurring with a pathogenic variant in BRCA2 (PMID: 10923033). While it is unknown if these variants are on the same or opposite chromosomes, this observation suggests that the c.291_296delATTAGA variant is not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 51371). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. In summary, this is a rare in-frame deletion with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Integrated Genetics/Laboratory Corporation of America RCV000589249 SCV000694646 uncertain significance not provided 2016-06-14 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.291_296delATTAGA (p.Glu97_Leu98del) variant results in an in-frame deletion. One in silico tool predicts a disease-causing outcome for this variant. This variant was absent in 120164 control chromosomes, and has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as a VUS. However, this variant has been found to co-occur in one LCA internal specimen with a pathogenic BRCA1 variant, c.4964_4982delCTGGCCTGACCCCAGAAGA, and in one patient reported in the BIC database with a pathogenic BRCA2 variant, c.4131_4132insTGAGGA (p.Thr1378_Gly1712delinsTer) in one individual. Taken together, the variant was classified as a variant of uncertain significance (VUS)-possibly benign until additional information becomes available.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113364 SCV000146517 uncertain significance Breast-ovarian cancer, familial 2 2001-02-16 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000113364 SCV000297517 uncertain significance Breast-ovarian cancer, familial 2 2011-08-30 no assertion criteria provided clinical testing

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