ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.3412G>A (p.Asp1138Asn) (rs587780249)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223506 SCV000276792 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Integrated Genetics/Laboratory Corporation of America RCV000587926 SCV000699723 uncertain significance not provided 2016-07-15 criteria provided, single submitter clinical testing Variant summary: The BRIP1 c.3412G>A (p.Asp1138Asn) variant involves the alteration of a conserved nucleotide. 3/5 in silico tools predict a benign outcome. 4/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1/120914 control chromosomes, which does not rule out the pathogenicity of this variant. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. In addition, one clinical diagnostic laboratory classified this variant as VUS. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000459206 SCV000547283 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2016-08-30 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 1138 of the BRIP1 protein (p.Asp1138Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (ExAC, <0.01%) but has not been reported in the literature in individuals with a BRIP1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging "; Align-GVGD: "Class C0"). In summary, this is a rare missense change with uncertain impact on protein function. There is no indication that this variant causes disease, but the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Mendelics RCV000709525 SCV000839350 uncertain significance Fanconi anemia, complementation group J 2018-07-02 criteria provided, single submitter clinical testing

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