ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2873T>A (p.Leu958Gln) (rs145859791)

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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 RCV000166915 SCV000217734 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-14 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000542669 SCV000633640 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces leucine with glutamine at codon 958 of the BRIP1 protein (p.Leu958Gln). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and glutamine. This variant is present in population databases (rs145859791, ExAC 0.01%). This variant has not been reported in the literature in individuals with BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 187210). 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.
Integrated Genetics/Laboratory Corporation of America RCV000588258 SCV000699706 uncertain significance not provided 2017-05-26 criteria provided, single submitter clinical testing Variant summary: The BRIP1 c.2873T>A (p.Leu958Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 1/121090 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRIP1 variant (0.0000625). This variant was reported in a cohort of HBOC patients (Yorczyk_Clinical Genetics_2014) and it was classifies as a VUS/unknown by two different laboratories (cited in ClinVar). Taken together, this variant is classified as VUS.
Color RCV000166915 SCV000905499 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-30 criteria provided, single submitter clinical testing

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