ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7222C>G (p.Pro2408Ala)

dbSNP: rs398122577
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000561315 SCV000664814 uncertain significance Hereditary cancer-predisposing syndrome 2021-03-02 criteria provided, single submitter clinical testing The p.P2408A variant (also known as c.7222C>G), located in coding exon 13 of the BRCA2 gene, results from a C to G substitution at nucleotide position 7222. The proline at codon 2408 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001300330 SCV001489467 uncertain significance Hereditary breast ovarian cancer syndrome 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces proline with alanine at codon 2408 of the BRCA2 protein (p.Pro2408Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is not present in population databases (ExAC 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: 480893). 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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