ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2273dup (p.Ala759fs) (rs587780236)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
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.
Ambry Genetics RCV000116138 SCV000216196 pathogenic Hereditary cancer-predisposing syndrome 2018-04-09 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Counsyl RCV000576781 SCV000677798 likely pathogenic Fanconi anemia, complementation group J; Neoplasm of ovary 2016-11-18 criteria provided, single submitter clinical testing
Invitae RCV000636094 SCV000757526 pathogenic Familial cancer of breast; Fanconi anemia, complementation group J 2019-12-11 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 individuals affected with prostate cancer (PMID: 27433846), endometrial cancer (PMID: 26681312), or ovarian cancer (PMID: 29368626). 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.
Color RCV000116138 SCV000911175 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000258967 SCV001248139 pathogenic not provided 2018-06-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001193525 SCV001362420 pathogenic Familial cancer of breast 2019-10-10 criteria provided, single submitter clinical testing Variant summary: BRIP1 c.2273dupT (p.Ala759SerfsX6) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (c.2392C>T, p.Arg798X; c.2400C>G, p.Tyr800X). The variant allele was found at a frequency of 8e-06 in 251216 control chromosomes (gnomAD). c.2273dupT has been reported in the literature in individuals affected with endometrial, prostate, ovarian or breast cancer (Susswein_2016, Pritchard_2016, Weber-Lassalle_2018). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Leiden Open Variation Database RCV000258967 SCV001364467 likely pathogenic not provided 2019-12-04 no assertion criteria provided curation Curator: Arleen D. Auerbach. Submitter to LOVD: Andreas Laner.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.