Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000574378 | SCV000668131 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-03 | criteria provided, single submitter | clinical testing | The p.V2758F variant (also known as c.8272G>T), located in coding exon 56 of the ATM gene, results from a G to T substitution at nucleotide position 8272. The valine at codon 2758 is replaced by phenylalanine, an amino acid with highly similar properties. This variant was identified in 1 of 13087 breast cancer cases and 0 of 5488 control individuals in the UK (Decker B et al. J Med Genet, 2017 Nov;54:732-741). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
Labcorp Genetics |
RCV002530301 | SCV003337104 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-09-21 | 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 create or strengthen a splice site. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 482735). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 2758 of the ATM protein (p.Val2758Phe). |