ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4942G>A (p.Ala1648Thr)

dbSNP: rs786202248
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164966 SCV000215658 likely benign Hereditary cancer-predisposing syndrome 2023-11-29 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000637534 SCV000758997 uncertain significance Hereditary breast ovarian cancer syndrome 2024-09-25 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1648 of the BRCA2 protein (p.Ala1648Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with colorectal cancer (PMID: 28135145). This variant is also known as 5170G>A. ClinVar contains an entry for this variant (Variation ID: 185525). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769698 SCV000901114 uncertain significance Breast and/or ovarian cancer 2017-02-07 criteria provided, single submitter clinical testing
GeneDx RCV002466457 SCV002762576 uncertain significance not provided 2022-06-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Observed in an individual with colorectal cancer (Yurgelun 2017); In silico analysis supports that this missense variant does not alter protein structure/function; Also known as 5170G>A; This variant is associated with the following publications: (PMID: 28135145)
University of Washington Department of Laboratory Medicine, University of Washington RCV000164966 SCV003852224 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).
Color Diagnostics, LLC DBA Color Health RCV000164966 SCV004362086 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-06 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 1648 of the BRCA2 protein. This variant is also known as 5170G>A in the literature. 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 been reported in an individual affected with colorectal cancer (PMID: 28135145). 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.
All of Us Research Program, National Institutes of Health RCV000239162 SCV004845754 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-10-02 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 1648 of the BRCA2 protein. This variant is also known as 5170G>A in the literature. 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 been reported in an individual affected with colorectal cancer (PMID: 28135145). 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.
Sharing Clinical Reports Project (SCRP) RCV000239162 SCV000297531 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2008-03-13 no assertion criteria provided clinical testing

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