ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2273dupT (p.Ala759Serfs) (rs587780236)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000116138 SCV000216196 pathogenic Hereditary cancer-predisposing syndrome 2018-04-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000116138 SCV000911175 pathogenic Hereditary cancer-predisposing syndrome 2018-03-25 criteria provided, single submitter clinical testing
Counsyl RCV000576781 SCV000677798 likely pathogenic Fanconi anemia, complementation group J; Neoplasm of ovary 2016-11-18 criteria provided, single submitter clinical testing
GeneDx RCV000258967 SCV000150047 pathogenic not provided 2016-05-13 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRIP1 is denoted c.2273dupT at the cDNA level and p.Ala759SerfsX6 (A759SfsX6) at the protein level. The normal sequence, with the base that is duplicated in braces, is CTGG[T]AGCA. The duplication causes a frameshift which changes an Alanine to a Serine at codon 759, and creates a premature stop codon at position 6 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. We consider this variant to be pathogenic.
Invitae RCV000636094 SCV000757526 pathogenic Familial cancer of breast; Fanconi anemia, complementation group J 2017-12-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ala759Serfs*6) in the BRIP1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs587780236, ExAC 0.001%). This variant has been reported in an individual affected with prostate cancer (PMID: 27433846), and an individual affected with endometrial cancer (PMID: 26681312). ClinVar contains an entry for this variant (Variation ID: 128170). 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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