ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9742A>C (p.Met3248Leu)

dbSNP: rs876659778
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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 RCV000215117 SCV000276598 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-29 criteria provided, single submitter clinical testing The p.M3248L variant (also known as c.9742A>C and 9970A>C), located in coding exon 26 of the BRCA2 gene, results from an A to C substitution at nucleotide position 9742. The methionine at codon 3248 is replaced by leucine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 150000 alleles tested) in our clinical cohort. This amino acid position is poorly conserved in available vertebrate species. 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 p.M3248L remains unclear.
All of Us Research Program, National Institutes of Health RCV003997975 SCV004842782 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2024-02-05 criteria provided, single submitter clinical testing This missense variant replaces methionine with leucine at codon 3248 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders in the literature. 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.

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