Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001012586 | SCV001173056 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-03 | criteria provided, single submitter | clinical testing | The p.G553R variant (also known as c.1657G>A), located in coding exon 10 of the ATM gene, results from a G to A substitution at nucleotide position 1657. The glycine at codon 553 is replaced by arginine, an amino acid with dissimilar properties. 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 this alteration remains unclear. |
Department of Pathology and Laboratory Medicine, |
RCV001355817 | SCV001550811 | uncertain significance | Malignant tumor of breast | no assertion criteria provided | clinical testing | The ATM p.Gly553Arg variant was not identified in the literature nor was it identified in the following databases: dbSNP, ClinVar, COGR, Cosmic, or LOVD 3.0, the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Gly553 residue is not conserved in mammals and 4 of 4 computational analyses (PolyPhen-2, SIFT, AlignGVGD, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 4 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |