ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.2345T>C (p.Ile782Thr)

gnomAD frequency: 0.00001  dbSNP: rs778758437
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000583295 SCV000689332 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000816110 SCV000956602 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2022-09-07 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 782 of the BRIP1 protein (p.Ile782Thr). This variant is present in population databases (rs778758437, gnomAD 0.02%). This missense change has been observed in individual(s) with Fanconi anemia (PMID: 30031030). ClinVar contains an entry for this variant (Variation ID: 491439). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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 RCV000583295 SCV001176059 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-11 criteria provided, single submitter clinical testing The p.I782T variant (also known as c.2345T>C), located in coding exon 15 of the BRIP1 gene, results from a T to C substitution at nucleotide position 2345. The isoleucine at codon 782 is replaced by threonine, an amino acid with similar properties. This variant was reported in a 2 year old Chinese patient with suspected Fanconi anemia due his having bone marrow failure with pancytopenia and polydactyly. In this individual, the variant was confirmed in trans with another missense alteration in FANCJ/BRIP1; however, functional analyses were not able to be completed in this case (Li N et al. Exp Hematol, 2018 10;66:32-41.e8). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001755973 SCV002006461 uncertain significance not provided 2019-05-30 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 30031030)
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV003493674 SCV004242898 uncertain significance not specified 2024-02-06 criteria provided, single submitter clinical testing

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