ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.589T>G (p.Ser197Ala)

dbSNP: rs730881505
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160025 SCV000210248 uncertain significance not provided 2013-11-27 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.589T>G at the cDNA level, p.Ser197Ala (S197A) at the protein level, and results in the change of a Serine to an Alanine (TCT>GCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Ser197Ala 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. This variant is a semi-conservative substitution of a neutral polar amino acid for a neutral non-polar one, altering a position that is well conserved throughout evolution and is not located in a known functional domain (UniProt). Multiple in silico algorithms predict that this variant may be damaging to protein structure and function. Based on currently available information, it is unclear whether BRCA2 Ser197Ala is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV002354402 SCV002653639 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-26 criteria provided, single submitter clinical testing The p.S197A variant (also known as c.589T>G), located in coding exon 6 of the BRCA2 gene, results from a T to G substitution at nucleotide position 589. The serine at codon 197 is replaced by alanine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003529996 SCV004323750 uncertain significance Hereditary breast ovarian cancer syndrome 2023-09-29 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 182178). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 197 of the BRCA2 protein (p.Ser197Ala).

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