Submissions for variant NM_032043.3(BRIP1):c.3118A>C (p.Lys1040Gln)

dbSNP: rs876659428

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000218508	SCV000275875	uncertain significance	Hereditary cancer-predisposing syndrome	2024-12-06	criteria provided, single submitter	clinical testing	The p.K1040Q variant (also known as c.3118A>C), located in coding exon 19 of the BRIP1 gene, results from an A to C substitution at nucleotide position 3118. The lysine at codon 1040 is replaced by glutamine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000231036	SCV000291033	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2022-05-05	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1040 of the BRIP1 protein (p.Lys1040Gln). This variant is not present in population databases (gnomAD 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: 231890). 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.
Color Diagnostics, LLC DBA Color Health	RCV000218508	SCV002051846	uncertain significance	Hereditary cancer-predisposing syndrome	2021-03-05	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with glutamine at codon 1040 of the BRIP1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Baylor Genetics	RCV003462482	SCV004217059	uncertain significance	Familial cancer of breast	2024-01-24	criteria provided, single submitter	clinical testing
GeneDx	RCV004719768	SCV005325501	uncertain significance	not provided	2024-01-10	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 11301010)