ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2998_3003del (p.Glu1000_Glu1001del) (rs80358333)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000048035 SCV000076048 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-06 criteria provided, single submitter clinical testing This variant, c.2998_3003delGAGGAA, results in the deletion of 2 amino acids of the BRCA1 protein (p.Glu1000_Glu1001del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in an individual affected with ovarian cancer (PMID: 11733976). In the literature, this variant is also known as c.3117del6. ClinVar contains an entry for this variant (Variation ID: 54743). 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, 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.
Ambry Genetics RCV000130154 SCV000184989 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000656789 SCV000210030 uncertain significance not provided 2018-06-21 criteria provided, single submitter clinical testing This in-frame deletion of six nucleotides in BRCA1 is denoted c.2998_3003delGAGGAA at the cDNA level and p.Glu1000_Glu1001del (E1000_E1001del) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GCTA[delGAGGAA]AACT. This variant, also known as EE1000del using alternative nomenclature, was observed in one individual with early-onset breast cancer unselected for family history (Peto 1999). This variant was not observed at a significant allele frequency in large population cohorts (Lek 2016). This deletion is located in the DNA binding domain and the RAD51 binding region (Chen 1998, Narod 2004). 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 BRCA1 Glu1000_Glu1001del to be a variant of uncertain significance.
Pathway Genomics RCV000111978 SCV000223748 uncertain significance Breast-ovarian cancer, familial 1 2014-10-30 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000159911 SCV000591417 uncertain significance not specified 2015-03-27 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000159911 SCV000600309 uncertain significance not specified 2017-04-28 criteria provided, single submitter clinical testing
Color RCV000130154 SCV000911051 likely benign Hereditary cancer-predisposing syndrome 2017-06-13 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000159911 SCV000918713 uncertain significance not specified 2017-11-06 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2998_3003delGAGGAA (p.Glu1000_Glu1001del) variant is an in-frame deletion in a non-repetitive region. The variant is outside of two well-known BCRT domains. One in silico tool (Mutation Taster) predicts a benign outcome for this variant. This variant was found in 5/246598 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.000045 (5/111478). This frequency is lower than the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). The variant has been reported in multiple affected individuals in literature and clinical databases, however without strong evidence for or against pathogenicity. Multiple clinical diagnostic laboratories/reputable databases have classified this variant as uncertain significance. Because of the absence of sufficient clinical information and the lack of functional studies, the variant is currently classified as a variant of uncertain significance (VUS) until additional information becomes available.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111978 SCV000144603 uncertain significance Breast-ovarian cancer, familial 1 2000-06-12 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000111978 SCV000297594 likely benign Breast-ovarian cancer, familial 1 2012-03-12 no assertion criteria provided clinical testing

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