ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1652C>T (p.Ala551Val) (rs375246789)

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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 RCV000130386 SCV000185243 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000130386 SCV000909774 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-22 criteria provided, single submitter clinical testing
GeneDx RCV000481084 SCV000569595 uncertain significance not provided 2016-03-14 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.1652C>T at the cDNA level, p.Ala551Val (A551V) at the protein level, and results in the change of an Alanine to a Valine (GCG>GTG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Ala551Val was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Alanine and Valine share similar properties, this is considered a conservative amino acid substitution. BRIP1 Ala551Val occurs at a position that is conserved across species and is located in the helicase domain (Cantor 2011). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether BRIP1 Ala551Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000636090 SCV000757522 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-11-13 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 551 of the BRIP1 protein (p.Ala551Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs375246789, ExAC 0.002%). This variant has not been reported in the literature in individuals with BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 141754). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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