Submissions for variant NM_000059.4(BRCA2):c.7034A>G (p.Gln2345Arg)

dbSNP: rs876661187

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000222987	SCV000279746	uncertain significance	not provided	2015-12-30	criteria provided, single submitter	clinical testing	This variant is denoted BRCA2 c.7034A>G at the cDNA level, p.Gln2345Arg (Q2345R) at the protein level, and results in the change of a Glutamine to an Arginine (CAG>CGG). Using alternate nomenclature, this variant would be defined as BRCA2 7262A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Gln2345Arg was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Gln2345Arg occurs at a position that is not conserved and is not located in a known functional domain. In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA2 Gln2345Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Illumina Laboratory Services, Illumina	RCV001112648	SCV001270332	uncertain significance	Fanconi anemia complementation group D1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV001112649	SCV001270333	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.