Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000565198 | SCV000667969 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-07-17 | criteria provided, single submitter | clinical testing | The p.D1563N variant (also known as c.4687G>A), located in coding exon 30 of the ATM gene, results from a G to A substitution at nucleotide position 4687. The aspartic acid at codon 1563 is replaced by asparagine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6493 samples (12986 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 180000 alleles tested) in our clinical cohort.This amino acid position is highly 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. |
Color Diagnostics, |
RCV000565198 | SCV001353166 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-21 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001246849 | SCV001420236 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-09-13 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 482623). This missense change has been observed in individual(s) with colorectal cancer (PMID: 27978560). This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1563 of the ATM protein (p.Asp1563Asn). |
Natera, |
RCV001246849 | SCV002083027 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-09-24 | no assertion criteria provided | clinical testing |