Submissions for variant NM_032043.3(BRIP1):c.3305A>G (p.Asp1102Gly)

dbSNP: rs748140041

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000554552	SCV000633664	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2022-04-13	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1102 of the BRIP1 protein (p.Asp1102Gly). This variant is present in population databases (rs748140041, gnomAD 0.0009%). 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: 461146). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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	RCV001182277	SCV001347674	uncertain significance	Hereditary cancer-predisposing syndrome	2019-10-01	criteria provided, single submitter	clinical testing	This missense variant replaces aspartic acid with glycine at codon 1102 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250836 chromosomes 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.
Ambry Genetics	RCV001182277	SCV002607095	uncertain significance	Hereditary cancer-predisposing syndrome	2022-07-14	criteria provided, single submitter	clinical testing	The p.D1102G variant (also known as c.3305A>G), located in coding exon 19 of the BRIP1 gene, results from an A to G substitution at nucleotide position 3305. The aspartic acid at codon 1102 is replaced by glycine, 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.