Submissions for variant NM_032043.3(BRIP1):c.241del (p.Glu81fs)

dbSNP: rs1292988272

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000780064	SCV000917086	likely pathogenic	Hereditary breast ovarian cancer syndrome	2020-08-17	criteria provided, single submitter	clinical testing	Variant summary: BRIP1 c.241delG (p.Glu81LysfsX20) 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. The variant allele was found at a frequency of 4e-06 in 251418 control chromosomes. To our knowledge, no occurrence of c.241delG in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Ambry Genetics	RCV001015489	SCV001176328	pathogenic	Hereditary cancer-predisposing syndrome	2019-02-04	criteria provided, single submitter	clinical testing	The c.241delG pathogenic mutation, located in coding exon 3 of the BRIP1 gene, results from a deletion of one nucleotide at nucleotide position 241, causing a translational frameshift with a predicted alternate stop codon (p.E81Kfs*20). 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	RCV001856183	SCV002144837	pathogenic	Familial cancer of breast; Fanconi anemia complementation group J	2024-05-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu81Lysfs*20) 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 0.003%). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 632726). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc.	RCV003336182	SCV004044467	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.