ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2324A>G (p.Asn775Ser) (rs571108955)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165749 SCV000216492 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-09 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
GeneDx RCV000656813 SCV000278901 uncertain significance not provided 2018-12-30 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.2324A>G at the cDNA level, p.Asn775Ser (N775S) at the protein level, and results in the change of an Asparagine to a Serine (AAT>AGT). This variant was observed in at least one individual with stomach adenocarcinoma and at least one individual with breast cancer (Lu 2015, Lin 2016). BRIP1 Asn775Ser was also identified in 1/62 healthy East Asian individuals undergoing whole genome sequencing (Bodian 2014); however, the participants in this study were younger than 50 years old, thus the unaffected status of this individual may not be significant. BRIP1 Asn775Ser was observed at an allele frequency of 0.16% (30/18,840) in individuals of East Asian ancestry in large population cohorts (Lek 2016). BRIP1 Asn775Ser is located within the helicase domain V (Cantor 2001). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRIP1 Asn775Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000165749 SCV000537560 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-26 criteria provided, single submitter clinical testing
Invitae RCV000475545 SCV000547288 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-09-05 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 775 of the BRIP1 protein (p.Asn775Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs571108955, ExAC 0.2%). This variant has been reported in the literature in an individual with breast cancer and/or a family history of breast and ovarian cancer (PMID: 26824983) and an individual affected with stomach adenocarcinoma (PMID: 26689913). ClinVar contains an entry for this variant (Variation ID: 133753). 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.
Counsyl RCV000663063 SCV000786124 uncertain significance Fanconi anemia, complementation group J; Neoplasm of ovary 2018-02-27 criteria provided, single submitter clinical testing
ITMI RCV000120397 SCV000084549 not provided not specified 2013-09-19 no assertion provided reference population
True Health Diagnostics RCV000165749 SCV000787965 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-07 no assertion criteria provided clinical testing

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