ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9353T>G (p.Met3118Arg)

dbSNP: rs56204128
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000216622 SCV000279890 uncertain significance not provided 2016-02-10 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9353T>G at the cDNA level, p.Met3118Arg (M3118R) at the protein level, and results in the change of a Methionine to an Arginine (ATG>AGG). Using alternate nomenclature, this variant would be defined as BRCA2 9581T>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Met3118Arg was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Methionine and Arginine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Met3118Arg occurs at a position that is not conserved and is located in the DNA binding domain (Yang 2002). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA2 Met3118Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV004601132 SCV005097490 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-23 criteria provided, single submitter clinical testing The p.M3118R variant (also known as c.9353T>G), located in coding exon 24 of the BRCA2 gene, results from a T to G substitution at nucleotide position 9353. The methionine at codon 3118 is replaced by arginine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
All of Us Research Program, National Institutes of Health RCV004804939 SCV005425847 uncertain significance BRCA2-related cancer predisposition 2024-03-05 criteria provided, single submitter clinical testing

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