ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.1156A>T (p.Lys386Ter)

dbSNP: rs730881635
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000505742 SCV000210840 likely pathogenic not provided 2017-07-21 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.1156A>T at the cDNA level and p.Lys386Ter (K386X) at the protein level. The substitution creates a nonsense variant, which changes a Lysine to a premature stop codon (AAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in several patients with breast cancer undergoing multigene panel testing (Susswein 2016, Frey 2017) and is considered likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001390434 SCV001592172 pathogenic Familial cancer of breast; Fanconi anemia complementation group J 2022-10-13 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 182347). For these reasons, this variant has been classified as Pathogenic. RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 26681312). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys386*) 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).
Ambry Genetics RCV002354404 SCV002623279 pathogenic Hereditary cancer-predisposing syndrome 2023-06-07 criteria provided, single submitter clinical testing The p.K386* pathogenic mutation (also known as c.1156A>T), located in coding exon 8 of the BRIP1 gene, results from an A to T substitution at nucleotide position 1156. This changes the amino acid from a lysine to a stop codon within coding exon 8. This alteration was identified in 1/10030 consecutive patients referred for evaluation by an NGS hereditary cancer panel (Susswein LR et al. Genet. Med., 2016 08;18:823-32). 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.
Myriad Genetics, Inc. RCV003335147 SCV004044317 pathogenic Familial cancer of breast 2023-06-01 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

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