ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9510C>G (p.Asp3170Glu)

dbSNP: rs876661072
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000218488 SCV000279453 uncertain significance not provided 2015-09-28 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9510C>G at the cDNA level, p.Asp3170Glu (D3170E) at the protein level, and results in the change of an Aspartic Acid to a Glutamic Acid (GAC>GAG). Using alternate nomenclature, this variant would be defined as BRCA2 9738C>G. This variant has not, to our knowledge, been published in the literature as being pathogenic or benign. BRCA2 Asp3170Glu 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 Aspartic Acid and Glutamic Acid share similar properties, this is considered a conservative amino acid substitution. BRCA2 Asp3170Glu occurs at a position that is not conserved and is not located in a known functional domain (Borg 2010, UniProt). 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 Asp3170Glu is pathogenic or benign. We consider it to be a variant of uncertain significance.
Mendelics RCV000989089 SCV001139268 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000709341 SCV004274694 uncertain significance Hereditary breast ovarian cancer syndrome 2023-06-19 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 3170 of the BRCA2 protein (p.Asp3170Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 234539). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. 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.

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