ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1425_1429del (p.Leu475fs) (rs768736851)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000576786 SCV000677881 likely pathogenic Fanconi anemia, complementation group J; Neoplasm of ovary 2017-02-14 criteria provided, single submitter clinical testing
GeneDx RCV000657382 SCV000779115 likely pathogenic not provided 2017-09-08 criteria provided, single submitter clinical testing This deletion of five nucleotides in BRIP1 is denoted c.1425_1429delAACTT at the cDNA level and p.Leu475PhefsX34 (L475FfsX34) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TCTT[delAACTT]TACA. The deletion causes a frameshift, which changes a Leucine to a Phenylalanine at codon 475 and creates a premature stop codon at position 34 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available evidence, we consider this deletion to be a likely pathogenic variant.
Color RCV000775422 SCV000909782 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Invitae RCV001063357 SCV001228198 pathogenic Familial cancer of breast; Fanconi anemia, complementation group J 2019-12-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu475Phefs*34) in the BRIP1 gene. It is expected to result in an absent or disrupted protein product. 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 not been reported in the literature in individuals with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 487424). Loss-of-function variants in BRIP1 are known to be pathogenic (PMID: 16116423, 17033622, 21964575). For these reasons, this variant has been classified as Pathogenic.

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