Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000480967 | SCV000566936 | uncertain significance | not provided | 2015-06-16 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.4871C>G at the cDNA level, p.Thr1624Ser (T1624S) at the protein level, and results in the change of a Threonine to a Serine (ACT>AGT). Using alternate nomenclature, this variant would be defined as BRCA2 5099C>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Thr1624Ser was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Threonine and Serine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Thr1624Ser occurs at a position that is not conserved and is located within the region of interaction with POLH (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRCA2 Thr1624Ser is pathogenic or benign. We consider it to be a variant of uncertain significance. |
University of Washington Department of Laboratory Medicine, |
RCV003157572 | SCV003852160 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
Ambry Genetics | RCV003157572 | SCV005027485 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-28 | criteria provided, single submitter | clinical testing | The p.T1624S variant (also known as c.4871C>G), located in coding exon 10 of the BRCA2 gene, results from a C to G substitution at nucleotide position 4871. The threonine at codon 1624 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |