Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000561226 | SCV000669242 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-02-01 | criteria provided, single submitter | clinical testing | The p.P283A variant (also known as c.847C>G), located in coding exon 7 of the CHEK2 gene, results from a C to G substitution at nucleotide position 847. This change occurs at the first base pair of coding exon 7. The proline at codon 283 is replaced by alanine, an amino acid with 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 6494 samples (12988 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 130000 alleles tested) in our clinical cohort. This nucleotide and amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be possibly damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |