ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.3096T>G (p.Ser1032Arg) (rs763162379)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164450 SCV000215092 uncertain significance Hereditary cancer-predisposing syndrome 2016-04-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000164450 SCV000909752 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-22 criteria provided, single submitter clinical testing
Counsyl RCV000412033 SCV000489883 uncertain significance Fanconi anemia, complementation group J 2016-07-11 criteria provided, single submitter clinical testing
Counsyl RCV000409520 SCV000489884 uncertain significance Neoplasm of ovary 2016-07-11 criteria provided, single submitter clinical testing
GeneDx RCV000520126 SCV000616667 uncertain significance not provided 2017-06-19 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.3096T>G at the cDNA level, p.Ser1032Arg (S1032R) at the proteinlevel, and results in the change of a Serine to an Arginine (AGT>AGG). This variant has not, to our knowledge, beenpublished in the literature as pathogenic or benign. BRIP1 Ser1032Arg was not observed at a significant allelefrequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek2016). Since Serine and Arginine differ in some properties, this is considered a semi-conservative amino acidsubstitution. BRIP1 Ser1032Arg occurs at a position that is not conserved and is located within the BRCA1 bindingdomain (Cantor 2011). In silico analyses predict that this variant is unlikely to alter protein structure or function. Basedon currently available evidence, it is unclear whether BRIP1 Ser1032Arg is a pathogenic or benign variant. Weconsider it to be a variant of uncertain significance.
Invitae RCV000636160 SCV000757592 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-09-11 criteria provided, single submitter clinical testing This sequence change replaces serine with arginine at codon 1032 of the BRIP1 protein (p.Ser1032Arg). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and arginine. This variant is present in population databases (rs763162379, ExAC 0.001%). This variant has not been reported in the literature in individuals with BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 185090). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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