ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.3525dup (p.Ile1176fs) (rs777367075)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000196468 SCV000255173 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-09-16 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the BRIP1 gene (p.Ile1176Tyrfs*13). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 74 amino acids of the BRIP1 protein. This variant is present in population databases (rs777367075, ExAC 0.002%). This variant has been reported in an individual affected with breast cancer (PMID: 26921362). ClinVar contains an entry for this variant (Variation ID: 216799). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000216896 SCV000274028 likely pathogenic Hereditary cancer-predisposing syndrome 2019-09-12 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Structural Evidence;Other data supporting pathogenic classification
GeneDx RCV000357297 SCV000329166 uncertain significance not provided 2016-06-21 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRIP1 is denoted c.3525dupT at the cDNA level and p.Ile1176TyrfsX13 (I1176YfsX13) at the protein level. The normal sequence, with the base that is duplicated in braces, is GAAC[T]ATAA. The duplication causes a frameshift which changes an Isoleucine to a Tyrosine at codon 1176 in the last exon of the protein, exon 20, and creates a premature stop codon at position 13 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause protein truncation. The last 74 amino acids of the protein are replaced by 12 incorrect amino acids, the clinical significance of which is unclear. The lost region is moderately conserved across species and is not within any known functional domain. This variant was not observed in approximately 6,500 individuals of European and African ancestry the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Based on currently available information, it is unclear whether this duplication is a pathogenic variant or a benign variant. We consider it to be a variant of uncertain significance.
Color RCV000216896 SCV000909745 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-11 criteria provided, single submitter clinical testing

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