ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.415T>G (p.Ser139Ala) (rs202072866)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000119157 SCV000153877 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-12-07 criteria provided, single submitter clinical testing This sequence change replaces serine with alanine at codon 139 of the BRIP1 protein (p.Ser139Ala). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and alanine. This variant is present in population databases (rs202072866, ExAC 0.009%). This variant has been reported in individuals affected with breast cancer (PMID: 18414782, 26534844, 26921362), as well as an individual affected with colorectal cancer (PMID: 28135145). This variant has also been observed in an unaffected control individual (PMID: 26315354). ClinVar contains an entry for this variant (Variation ID: 132712). 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: "Possibly 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.
Ambry Genetics RCV000131152 SCV000186094 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000589911 SCV000278893 uncertain significance not provided 2018-07-05 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.415T>G at the cDNA level, p.Ser139Ala (S139A) at the protein level, and results in the change of a Serine to an Alanine (TCT>GCT). This variant has been observed in individuals with breast cancer and in an individual with colorectal cancer, but has also been observed in a healthy control subject (Gu?nard 2008, Ramus 2015, Lu 2015, Easton 2016, Li 2016, Yurgelun 2017). BRIP1 Ser139Ala was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRIP1 Ser139Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000411415 SCV000489997 uncertain significance Fanconi anemia, complementation group J 2016-09-13 criteria provided, single submitter clinical testing
Counsyl RCV000412061 SCV000489998 uncertain significance Neoplasm of ovary 2016-09-13 criteria provided, single submitter clinical testing
Color RCV000131152 SCV000684279 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589911 SCV000699707 uncertain significance not provided 2016-03-14 criteria provided, single submitter clinical testing
GeneKor MSA RCV000131152 SCV000821965 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Mendelics RCV000411415 SCV000839399 uncertain significance Fanconi anemia, complementation group J 2018-07-02 criteria provided, single submitter clinical testing
Mendelics RCV000990035 SCV001140799 uncertain significance Familial cancer of breast 2019-05-28 criteria provided, single submitter clinical testing

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