Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001071690 | SCV001237008 | uncertain significance | Ataxia-telangiectasia syndrome | 2019-12-16 | 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, but this prediction has not been confirmed by published transcriptional studies. 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"). This variant has not been reported in the literature in individuals with ATM-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with glycine at codon 20 of the ATM protein (p.Ala20Gly). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and glycine. |
| Ambry Genetics | RCV002355103 | SCV002657155 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-06-01 | criteria provided, single submitter | clinical testing | The c.59C>G variant (also known as p.A20G), located in coding exon 1 of the ATM gene, results from a C to G substitution at nucleotide position 59. The alanine at codon 20 is replaced by glycine, an amino acid with similar properties. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |