ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3059_3060del (p.Leu1019_Ser1020insTer) (rs876661270)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000661886 SCV000784212 pathogenic Breast-ovarian cancer, familial 2 2017-12-15 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000217537 SCV000279942 pathogenic not provided 2016-03-02 criteria provided, single submitter clinical testing This deletion of 2 nucleotides is denoted BRCA2 c.3059_3060delCT at the cDNA level and p.Ser1020Ter (S1020X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 3287_3288delCT. The normal sequence, with the bases that are deleted in braces, is CTCT[CT]GAAC. The deletion creates a nonsense variant, which changes a Serine to a premature stop codon. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193838 SCV001362984 likely pathogenic Hereditary breast and ovarian cancer syndrome 2019-08-12 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3059_3060delCT (p.Ser1020X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (c.3199delA, p.Thr1067fsX10; c.3264dupT, p.Gln1089fsX10; c.3680_3681delTG, p.Leu1227fsX5). The variant was absent in 250546 control chromosomes (gnomAD). To our knowledge, no occurrence of c.3059_3060delCT in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submissions including one expert panel (ENIGMA) (evaluation after 2014) classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV001193838 SCV001587833 pathogenic Hereditary breast and ovarian cancer syndrome 2020-09-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1020*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 234872). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
True Health Diagnostics RCV000664260 SCV000787926 pathogenic Hereditary cancer-predisposing syndrome 2018-01-05 no assertion criteria provided clinical testing

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