Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000166938 | SCV000217758 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-08 | criteria provided, single submitter | clinical testing | The p.N108S variant (also known as c.323A>G), located in coding exon 3 of the BRCA2 gene, results from an A to G substitution at nucleotide position 323. The asparagine at codon 108 is replaced by serine, an amino acid with highly similar properties. This alteration has been reported in one patient who was diagnosed with high-grade serous ovarian carcinoma in her 70s without family history of breast or ovarian cancer in any first- or second-degree relatives from a cohort of 158 Brazilian ovarian cancer patients (Cotrim DP et al. BMC Cancer, 2019 Jan;19:4). This amino acid position is poorly 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. |
Gene |
RCV000221445 | SCV000279279 | uncertain significance | not provided | 2018-05-16 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.323A>G at the cDNA level, p.Asn108Ser (N108S) at the protein level, and results in the change of an Asparagine to a Serine (AAT>AGT). Using alternate nomenclature, this variant would be defined as BRCA2 551A>G. This variant was observed in an individual during a validation study of a high-throughput protocol for variant identification; however, no clinical information was provided (Hondow 2011). BRCA2 Asn108Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Asn108Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Illumina Clinical Services Laboratory, |
RCV000315720 | SCV000383610 | uncertain significance | Fanconi anemia, complementation group D1 | 2018-01-13 | 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 Clinical Services Laboratory, |
RCV000077298 | SCV000383611 | uncertain significance | Breast-ovarian cancer, familial 2 | 2018-01-13 | 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. |
Counsyl | RCV000077298 | SCV000488230 | uncertain significance | Breast-ovarian cancer, familial 2 | 2016-02-08 | criteria provided, single submitter | clinical testing | |
Color Health, |
RCV000166938 | SCV000683538 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-22 | criteria provided, single submitter | clinical testing | |
Sharing Clinical Reports Project |
RCV000077298 | SCV000109095 | uncertain significance | Breast-ovarian cancer, familial 2 | 2013-10-07 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000077298 | SCV000146593 | uncertain significance | Breast-ovarian cancer, familial 2 | 1998-06-22 | no assertion criteria provided | clinical testing |