ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.66A>G (p.Ala22=)

dbSNP: rs1555280115
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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 RCV001025547 SCV001187751 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-24 criteria provided, single submitter clinical testing The c.66A>G variant (also known as p.A22A), located in coding exon 1 of the BRCA2 gene, results from an A to G substitution at nucleotide position 66. This nucleotide substitution does not change the alanine at codon 22. However, this change occurs in the second last base pair of coding exon 1, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001862329 SCV002292143 uncertain significance Hereditary breast ovarian cancer syndrome 2020-12-23 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 826559). This variant is not present in population databases (ExAC no frequency). This sequence change affects codon 22 of the BRCA2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the BRCA2 protein.

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