ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.143A>G (p.Glu48Gly)

dbSNP: rs1478651557
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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 RCV001011582 SCV001171919 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-22 criteria provided, single submitter clinical testing The p.E48G variant (also known as c.143A>G), located in coding exon 2 of the BRCA2 gene, results from an A to G substitution at nucleotide position 143. The glutamic acid at codon 48 is replaced by glycine, an amino acid with similar properties. A minigene assay demonstrated that this alteration results in skipping of coding exon 2 in 26.9% of transcripts (Fraile-Bethencourt E et al. J Pathol, 2019 08;248:409-420). This amino acid position is well 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 this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001860672 SCV002207168 uncertain significance Hereditary breast ovarian cancer syndrome 2021-10-18 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. RNA analysis indicates that this missense change does not impact mRNA splicing (PMID: 30883759, 32641407). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 819217). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glycine at codon 48 of the BRCA2 protein (p.Glu48Gly). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and glycine.

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