Submissions for variant NM_032043.3(BRIP1):c.589T>C (p.Ser197Pro)

dbSNP: rs530897769

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001024659	SCV001186714	uncertain significance	Hereditary cancer-predisposing syndrome	2024-06-12	criteria provided, single submitter	clinical testing	The p.S197P variant (also known as c.589T>C), located in coding exon 5 of the BRIP1 gene, results from a T to C substitution at nucleotide position 589. The serine at codon 197 is replaced by proline, an amino acid with similar properties. 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	RCV001215301	SCV001387038	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2022-03-29	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 197 of the BRIP1 protein (p.Ser197Pro). This variant is present in population databases (rs530897769, gnomAD 0.02%). 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: 826041). 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: "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.
GeneDx	RCV001593190	SCV001824278	uncertain significance	not provided	2019-10-10	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Neuberg Centre For Genomic Medicine, NCGM	RCV003448361	SCV004176595	uncertain significance	Familial cancer of breast	2023-03-01	criteria provided, single submitter	clinical testing	The missense c.589T>C (p.Ser197Pro) variant in BRIP1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Ser197Pro variant has allele frequency 0.002% in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid change p.Ser197Pro in BRIP1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Ser at position 197 is changed to a Pro changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).
Baylor Genetics	RCV003448361	SCV004214750	uncertain significance	Familial cancer of breast	2023-09-15	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV001024659	SCV005045352	uncertain significance	Hereditary cancer-predisposing syndrome	2024-01-23	criteria provided, single submitter	clinical testing