ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.128_131del (p.Leu43fs)

dbSNP: rs1064794202
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486415 SCV000568180 pathogenic not provided 2023-06-08 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27779110, 26315354, 30733081, 32295079, 29025585, 35171259, 29922827)
Ambry Genetics RCV001010722 SCV001170959 pathogenic Hereditary cancer-predisposing syndrome 2024-10-03 criteria provided, single submitter clinical testing The c.128_131delTGTT pathogenic mutation, located in coding exon 2 of the BRIP1 gene, results from a deletion of 4 nucleotides at nucleotide positions 128 to 131, causing a translational frameshift with a predicted alternate stop codon (p.L43Wfs*11). In one study, this mutation was detected in an unaffected individual who had two first-degree relatives with ovarian cancer (Ramus SJ et al. J. Natl. Cancer Inst. 2015 Nov;107). In another study, this alteration was identified in an individual affected with gastric cancer (Slavin T et al. Cancer Genet, 2017 Oct;216-217:111-119). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV001066099 SCV001231096 pathogenic Familial cancer of breast; Fanconi anemia complementation group J 2023-10-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu43Trpfs*11) in the BRIP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRIP1 are known to be pathogenic (PMID: 16116423, 17033622, 21964575). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with ovarian cancer (PMID: 26315354). ClinVar contains an entry for this variant (Variation ID: 419951). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health RCV001010722 SCV001356021 pathogenic Hereditary cancer-predisposing syndrome 2022-06-13 criteria provided, single submitter clinical testing This variant deletes 4 nucleotides in exon 3 of the BRIP1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with familial ovarian cancer (PMID: 26315354). This variant has been identified in 1/251410 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRIP1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Sema4, Sema4 RCV001010722 SCV002531341 pathogenic Hereditary cancer-predisposing syndrome 2021-08-16 criteria provided, single submitter curation
Myriad Genetics, Inc. RCV003335356 SCV004043472 pathogenic Familial cancer of breast 2023-05-30 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Baylor Genetics RCV003335356 SCV004217084 pathogenic Familial cancer of breast 2023-06-14 criteria provided, single submitter clinical testing
CZECANCA consortium RCV001271070 SCV001451896 pathogenic Breast and/or ovarian cancer 2019-06-11 no assertion criteria provided clinical testing

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