Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587975 | SCV000694499 | uncertain significance | not provided | 2016-04-04 | criteria provided, single submitter | clinical testing | Variant Summary: Variant of interest impacts a non-conserved nucleotide and results in a replacement of a medium size and polar Threonine (T) with a small size and hydrophobic Alanine (A). 3/4 in silico tools predict the variant to be benign, and to our knowledge studies assessing the impact of the variant in isolation on the function of the protein were not published at the time of variant classification. It is absent from the large and broad cohorts of the ExAC project and has not been cited in patients from the literature. However, a nonsense BRCA2 variant located upstream of the variant of interest (p.Lys3326Ter) is a well know benign variant, indicating that Thr3388 is a non-essential amino acid for BRCA2 function, and thus p.Thr3388Ala is likely in the benign spectrum. Moreover, a clinical laboratory classified the variant as Likely benign via ClinVar (without evidence to independently evaluate). Considering all evidence, the variant was classified as a VUS-possibly benign/benign until more information becomes available. |
| Labcorp Genetics |
RCV001443475 | SCV001646447 | likely benign | Hereditary breast ovarian cancer syndrome | 2024-08-28 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV001804835 | SCV002052175 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-07 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with alanine at codon 3388 of the BRCA2 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. |
| Ambry Genetics | RCV001804835 | SCV002634919 | likely benign | Hereditary cancer-predisposing syndrome | 2019-04-27 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Sharing Clinical Reports Project |
RCV000082880 | SCV000114954 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2012-05-01 | no assertion criteria provided | clinical testing |