ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.5C>T (p.Ser2Phe)

dbSNP: rs751194347
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000562127 SCV000668933 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-24 criteria provided, single submitter clinical testing The p.S2F variant (also known as c.5C>T), located in coding exon 1 of the BRIP1 gene, results from a C to T substitution at nucleotide position 5. The serine at codon 2 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 175000 alleles tested) in our clinical cohort. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001362707 SCV001558737 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2021-08-26 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 2 of the BRIP1 protein (p.Ser2Phe). The serine residue is moderately conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 483179). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV004553276 SCV005043783 uncertain significance Familial cancer of breast 2024-05-15 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 2 of the BRIP1 protein (p.Ser2Phe). The serine residue is moderately conserved and there is a large physicochemical difference between serine and phenylalanine. This amino acid position is well conserved (PhyloP=7.91) . This variant is not present in population databases (gnomAD). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 483179).In addition, the in silico prediction for this alteration is inconclusive. 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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