ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.2935A>G (p.Lys979Glu)

gnomAD frequency: 0.00001  dbSNP: rs730881627
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212331 SCV000210828 uncertain significance not provided 2024-06-18 criteria provided, single submitter clinical testing Observed in individuals with ovarian cancer or breast cancer in published literature (PMID: 26315354, 26921362, 31822495); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26315354, 26921362, 31822495, 11301010, 34326862)
Ambry Genetics RCV000160326 SCV000217257 likely benign Hereditary cancer-predisposing syndrome 2024-04-19 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV000205057 SCV000260094 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2025-01-30 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 979 of the BRIP1 protein (p.Lys979Glu). This variant is present in population databases (rs730881627, gnomAD 0.002%). This missense change has been observed in individual(s) with ovarian cancer (PMID: 26315354, 26921362, 31822495). ClinVar contains an entry for this variant (Variation ID: 182336). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRIP1 protein function with a negative predictive value of 95%. 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.
Color Diagnostics, LLC DBA Color Health RCV000160326 SCV000911030 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-30 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid at codon 979 of the BRIP1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with breast and ovarian cancer in the literature (PMID: 26315354, 31822495). This variant has been identified in 3/250862 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV002254684 SCV002525940 uncertain significance Fanconi anemia complementation group J 2022-05-16 criteria provided, single submitter clinical testing The BRIP1 c.2935A>G (p.Lys979Glu) missense change has a maximum subpopulation frequency of 0.0018% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). It is predicted to have a benign effect on protein function (BP4), but to our knowledge this prediction has not been confirmed by functional studies. This variant has been reported in individuals with breast cancer (PMID: 26921362, 31822495) and ovarian cancer (PMID: 26315354). To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: BP4.
Sema4, Sema4 RCV000160326 SCV002533659 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-08 criteria provided, single submitter curation
Baylor Genetics RCV004567202 SCV005059227 uncertain significance Familial cancer of breast 2024-03-05 criteria provided, single submitter clinical testing

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